The region around Chennai has served as an important administrative, military, and economic centre dating back to the first century. It has been ruled by South Indian kingdoms, notably the Pallava, the Chola, the Pandya, and Vijaynagar empires. The town of Mylapore, now part of the metropolis, was once a major port of the Pallava kingdom. When the Portuguese arrived in 1522, they built a port and named it São Tomé, after the Christian apostle St. Thomas, who is believed to have preached there between the years 52 and 70. The region then passed into the hands of the Dutch, who established themselves near Pulicat just north of the city in 1612.

On 22 August 1639, Francis Day of the British East India Company obtained a small strip of land in the Coromandel Coast from the Aravidu line of Vijayanagara King, Peda Venkata Raya (a.k.a. Venkata III) in Chandragiri. The region was ruled by Damerla Venkatapathy, the Nayak of Vandavasi. He granted permission to the British to build a factory and warehouse for their trading activities. A year later, Fort St George was built, which subsequently became the nucleus around which the colonial city grew. In 1746, Fort St George and Madras were captured by the French under General La Bourdonnais, the Governor of Mauritius, who plundered the town and its outlying villages. The British regained control of the town in 1749 through the Treaty of Aix-la-Chapelle and subsequently fortified the base to withstand further attacks from the French and Hyder Ali, the Sultan of Mysore. By the late 18th century, the British had conquered most of the region around Tamil Nadu and the northern modern-day states of Andhra Pradesh and Karnataka to establish the Madras Presidency, whose capital was Madras. Under British rule the city grew into a major urban centre and naval base. With the advent of railways in India in the late 19th century, it was connected to other important cities such as Mumbai (formerly known as Bombay) and Kolkata (formerly Calcutta), facilitating communication and trade with the hinterland. It was the only Indian city to be attacked by the Central Powers during World War I, when an oil depot was shelled by the German light cruiser SMS Emden on September 22, 1914, causing disruption to shipping.

After independence in 1947, the city became the capital of Madras State, which was renamed Tamil Nadu in 1969. From 1965 to 1967, Chennai was an important base for the Tamil agitation against the imposition of Hindi. In 2004, the Indian Ocean tsunami lashed the shores of Chennai, killing many and permanently altering the coastline