Although these dynasties were never conquered by outside powers, there were still significant diplomatic contacts between them and kingdoms to the north. They were mentioned on the pillars of Ashoka.

These rulers sponsored some of the earliest Tamil literature. The oldest Sangam work we have knowledge of is the Tolkappiyam, a book of Tamil grammar. Most Sangam literature dealt with themes of love and war. In these poems, a glimpse of Tamil society at the time can be glimpsed. The land was fertile, and people pursued different occupations depending on what regions they were in. Their gods included figures such as Seyyon and Kotravai, who were worshipped at different places. The rulers patronised Buddhism and Jainism, and starting in the CE period references to Vedic customs begin to grow.

Significant trade was also undertaken with the outside world. Much commerce from the Romans and Han China converged in the Tamil region, and the seaports of Muziris and Korkai were very popular destinations. One of the most prized goods from Tamilkam was spices such as black pepper, but other spices, pearls and silk were also widely traded there.

Starting in 300, however, there was a significant drop in Sangam literature. Some have attributed this to the Kalabhras, a dynasty which conquered much of Tamilkam during that time. Historians have speculated these rulers were antagonistic towards the astika schools which were dominant in later centuries, which is why later texts always portray their rule in a bad light, if at all. During their rule, Samanar traditions greatly impacted literature written during this time. Literacy was widespread and epics such as the Cilappatikaram were written. The most prominent of these works is the Tirukkuṟaḷ written by Valluvar, a collection of couplets covering all aspects of life from ethics to love. This text is still treated with great reverence by those in the present-day. Around the 7th century CE, the Kalabhras were overthrown by the Pandyas and Cholas, who continued to patronise Buddhists and Jains before the Saiva and Vaishnava revivalism in the Bhakti movement.

They had extensive trade links with the southeast Asian maritime empires of Srivijaya and their successors, as well as contacts, even formal diplomatic contacts, reaching as far as the Roman Empire. During the 13th century, Marco Polo mentioned the Pandyas as the richest empire in existence. Temples such as the Meenakshi Amman Temple at Madurai and Nellaiappar Temple at Tirunelveli are the best examples of Pandyan temple architecture. The Pandyas excelled in both trade and literature. They controlled the pearl fisheries along the south coast of India, between Sri Lanka and India, which produced some of the finest pearls in the known ancient world.

The Cholas were prolific temple builders right from the times of the first medieval King Vijayalaya Chola. These are the earliest specimen of Dravidian temples under the Cholas. His son Aditya I built several temples around the Kanchi and Kumbakonam regions. The Cholas went on to becoming a great power and built some of the most imposing religious structures in their lifetime and they also renovated temples and buildings of the Pallavas, acknowledging their common socio-religious and cultural heritage. The celebrated Nataraja temple at Chidambaram and the Ranganathaswamy Temple at Srirangam, Tiruchirappalli, held special significance for the Cholas which have been mentioned in their inscriptions as their tutelary deities. Rajaraja Chola I and his son Rajendra Chola built temples such as the Brihadeshvara Temple of Thanjavur and Brihadeshvara Temple of Gangaikonda Cholapuram, the Airavatesvara Temple of Darasuram and the Sarabeswara (Shiva) Temple, also called the Kampahareswarar Temple at Thirubhuvanam, the last two temples being located near Kumbakonam. The first three of the above four temples are titled Great Living Chola Temples among the UNESCO World Heritage Sites.

Europeans started to establish trade centers during the 17th century in the eastern coastal regions. Around 1609, the Dutch established a settlement in Pulicat, while the Danes had their establishment in Tharangambadi also known as Tranquebar. In 1639, the British, under the East India Company, established a settlement further south of Pulicat, in present-day Chennai. British constructed Fort St. George and established a trading post at Madras. The office of mayoralty of Madras was established in 1688. The French established trading posts at Pondichéry by 1693. The British and French were competing to expand the trade in the northern parts of Tamil Nadu which also witnessed many battles like Battle of Wandiwash as part of the Seven Years' War. British reduced the French dominions in India to Puducherry. Nawabs of the Carnatic bestowed tax revenue collection rights on the East India Company for defeating the Kingdom of Mysore. Muhammad Ali Khan Wallajah surrendered much of his territory to the East India Company which firmly established the British in the northern parts. In 1762, a tripartite treaty was signed between Thanjavur Maratha, Carnatic, and the British by which Thanjavur became a vassal of the Nawab of the Carnatic which eventually ceded to the British.

In the south, Nawabs granted taxation rights to the British which led to conflicts between British and the Palaiyakkarar, which resulted in series of wars called Polygar war to establish independent states by the aspiring Palaiyakkarar. Puli Thevar was one of the earliest opponents of the British rule in South India. Thevar's prominent exploits were his confrontations with Marudhanayagam, who later rebelled against the British in the late 1750s and early 1760s. Rani Velu Nachiyar, was the first woman freedom fighter of India and Queen of Sivagangai. She was drawn to war after her husband Muthu Vaduganatha Thevar (1750–1772), King of Sivaganga was murdered at Kalayar Kovil temple by British. Before her death, Queen Velu Nachi granted powers to the Maruthu brothers to rule Sivaganga. Kattabomman (1760–1799), Palaiyakkara chief of Panchalakurichi who fought the British in the First Polygar War. He was captured by the British at the end of the war and hanged near Kayattar in 1799. Veeran Sundaralingam (1700–1800) was the General of Kattabomman Nayakan's palayam, who died in the process of blowing up a British ammunition dump in 1799 which killed more than 150 British soldiers to save Kattapomman Palace. Oomaithurai, younger brother of Kattabomman, took asylum under the Maruthu brothers, Periya Marudhu and Chinna Marudhu and raised an army. They formed a coalition with Dheeran Chinnamalai and Kerala Varma Pazhassi Raja, which fought the British in Second Polygar Wars. Dheeran Chinnamalai (1756–1805), Polygar chieftain of Kongu and ally of Tipu Sultan who fought the British in the Second Polygar War. After winning the Polygar wars in 1801, the East India Company consolidated most of southern India into the Madras Presidency.

During the administration of Governor George Harris (1854–1859) measures were taken to improve education and increase the representation of Indians in the administration. Legislative powers are given to the Governor's council under the Indian Councils Act 1861 and 1909 Minto-Morley Reforms eventually led to the establishment of the Madras Legislative Council. Failure of the summer monsoons and administrative shortcomings of the Ryotwari system resulted in two severe famines in the Madras Presidency, the Great Famine of 1876–78 and the Indian famine of 1896–97 killed millions of Tamils.The famine led to the migration of many Tamil peasants as bonded labourers for the British to countries like Malaysia and Mauritius, which eventually formed the present Tamil diaspora.

Tamil Nadu provided a significant number of freedom fighters to the Independence struggle such as V. O. Chidambaram Pillai and Bharatiyar. The Tamils (particularly Tamil Malaysians) formed a significant percentage of the members of the Indian National Army (INA), founded by Subhas Chandra Bose to fight the British colonial rule in India. Lakshmi Sahgal from Tamil Nadu was a prominent leader in the INA's Rani of Jhansi Regiment.

In 1916 Dr. T.M. Nair and Rao Bahadur Thygaraya Chetty released the Non-Brahmin Manifesto and helped to form the Justice Party, an organisation that sought to reduce Brahmin domination of the civil service. The party won the legislative assembly elections of 1921, which was boycotted by the Congress. This party implemented reservations in government jobs and education for non-Brahmins in 1926, and stayed in power for 13 years. The other main movement was the self-respect movement of E. V. Ramaswamy, better known as Periyar. Periyar campaigned for an end to what he saw as Aryan domination of culture and life in Tamil Nadu. To this end, he became an advocate of rationalism, and campaigned against the caste system, religion, and superstition.

Further steps towards eventual self-rule were taken in 1935 when the British Government passed the Government of India Act 1935. Fresh local elections were held and in Tamil Nadu the Congress party captured power defeating the Justice party. In 1938, Periyar along with C. N. Annadurai launched an agitation against the Congress ministry's decision to introduce the teaching of Hindi in schools. Thereafter, the Justice party was taken over by Periyar who renamed it Dravidar Kazhagam and took it out of electoral politics. The group became an advocate for a separate Dravida Nadu during discussions of the partition of India.

The eastern parts are fertile coastal plains and the northern parts are a mix of hills and plains. The central and the south-central regions are arid plains and receive less rainfall than the other regions.

Tamil Nadu has the country's third-longest coastline at about 906.9 km. Pamban Island and a group of smaller limestone shoals make up the northern portion of Ram Setu, which was formerly a natural bridge linking India with Sri Lanka. Tamil Nadu's coastline bore the brunt of the 2004 Indian Ocean tsunami when it hit India, which caused 7,793 direct deaths in the state. Tamil Nadu falls mostly in a region of low seismic hazard with the exception of the western border areas that lie in a low to moderate hazard zone; as per the 2002 Bureau of Indian Standards (BIS) map, Tamil Nadu falls in Zones II and III. Historically, parts of this region have experienced seismic activity in the M5.0 range.

This includes 1,559 species of medicinal plants, 533 endemic species, 260 species of wild relatives of cultivated plants and 230 red-listed species. The gymnosperm diversity of the country is 64 species of which Tamil Nadu has four indigenous species and about 60 introduced species. The Pteridophytes diversity of India includes 1,022 species of which Tamil Nadu has about 184 species. Vast numbers of bryophytes, lichen, fungi, algae, and bacteria are among the wild plant diversity of Tamil Nadu.

Common plant species include the state tree: palmyra palm, eucalyptus, rubber, cinchona, clumping bamboos (Bambusa arundinacea), common teak, Anogeissus latifolia, Indian laurel, grewia, and blooming trees like Indian laburnum, ardisia, and solanaceae. Rare and unique plant life includes Combretum ovalifolium, ebony (Diospyros nilagrica), Habenaria rariflora (orchid), Alsophila, Impatiens elegans, Ranunculus reniformis, and royal fern.

The Gulf of Mannar Biosphere Reserve established in 1986 is a marine ecosystem with seaweed seagrass communities, coral reefs, salt marshes, and mangrove forests. The Nilgiri Biosphere Reserve located in the Western Ghats and Nilgiri Hills comprises part of adjoining states of Kerala and Karnataka. The Agasthyamala Biosphere Reserve is in the southwest of the state bordering Kerala in the Western Ghats. Tamil Nadu is home to five declared national parks located in Anamalai, Mudumalai, Mukurthi, Gulf of Mannar, Guindy located in the center of Chennai City and Vandalur located in South Chennai. Sathyamangalam Tiger Reserve, Mukurthi National Park and Kalakkad Mundanthurai Tiger Reserve are the tiger reserves in the state.

The state has 51,837,507 literates, making the literacy rate 80.33 per cent. There are a total of 27,878,282 workers, comprising 4,738,819 cultivators, 6,062,786 agricultural labourers, 1,261,059 in house hold industries, 11,695,119 other workers, 4,120,499 marginal workers, 377,220 marginal cultivators, 2,574,844 marginal agricultural labourers, 238,702 marginal workers in household industries and 929,733 other marginal workers.

India has a human development index calculated as 0.619, while the corresponding figure for Tamil Nadu is 0.736, placing it among the top states in the country. The life expectancy at birth for males is 65.2 years and for females it is 67.6 years. However, it has a high level of poverty, especially in rural areas. In 2004–2005, the poverty line was set at ₹351.86/month for rural areas and ₹547.42/month for urban areas. Poverty in the state dropped from 51.7 per cent in 1983 to 21.1 per cent in 2001. For the period 2004–2005, the Trend in Incidence of Poverty in the state was 22.5 per cent compared with the national figure of 27.5 per cent. The World Bank is currently assisting the state in reducing poverty, high drop-out and low completion of secondary schools continue to hinder the quality of training in the population. Other problems include class, gender, inter-district, and urban-rural disparities. Based on URP – Consumption for the period 2004–2005, the percentage of the state's population below the poverty line was 27.5 per cent. The Oxford Poverty and Human Development Initiative ranks Tamil Nadu to have a Multidimensional Poverty Index of 0.141, which is in the level of Ghana among the developing countries. Corruption is a major problem in the state with Transparency International ranking it the second most corrupt among the states of India.

Services contribute to 45 per cent of the economic activity in the state, followed by manufacturing at 34 per cent and agriculture at 21 per cent. The government is the major investor in the state with 51 per cent of total investments, followed by private Indian investors at 29.9 per cent and foreign private investors at 14.9 per cent. Tamil Nadu has a network of about 113 industrial parks and estates offering developed plots with supporting infrastructure. According to the publications of the Tamil Nadu government, the Gross State Domestic Product at Constant Prices (The base year 2004–2005) for the year 2011–2012 is ₹4.281 trillion (US$56 billion), an increase of 9.39 per cent over the previous year. The per capita income at the current price is ₹72,993.

Tamil Nadu has six Nationalized Home Banks which originated in this state; Two government-sector banks Indian Bank and Indian Overseas Bank in Chennai, and four private-sector banks City Union Bank in Kumbakonam, Karur Vysya Bank, Lakshmi Vilas Bank in Karur, and Tamilnad Mercantile Bank Limited in Tuticorin.