The region around Coimbatore was ruled by the Sangam Cheras dyansty and it served as the eastern entrance to the Palakkad Gap, the principal trade route between the west coast and Tamil Nadu. The Kossar tribe mentioned in the second century CE Tamil epic Silappathikaram and other poems in Sangam literature is associated with the Coimbatore region (Kongu Nadu). The region was in the middle of a Roman trade route that extended from Muziris to Arikamedu. The medieval Cholas conquered the Kongu Nadu in the 10th century CE. A Chola highway called Rajakesari Peruvazhi ran through the region. Much of Tamil Nadu came under the rule of the Vijayanagara Empire by the 15th century. In the 1550s, Madurai Nayaks who were the military governors of the Vijaynagara Empire took control of the region. After the Vijayanagara Empire fell in the 17th century, the Madurai Nayaks established their state as an independent kingdom. The Nayaks introduced the Palayakkarar system under which Kongu nadu region was divided into 24 Palayams.
In the later part of the 18th century, the region came under the Kingdom of Mysore, following a series of wars with the Madurai Nayak Dynasty. After the defeat of Tipu Sultan in the Anglo-Mysore Wars, the British East India Company annexed Coimbatore to the Madras Presidency in 1799. The Coimbatore region played a prominent role in the Second Poligar War (1801) when it was the area of operations of Dheeran Chinnamalai.
In 1804, Coimbatore district was newly carved out and Coimbatore was established as the capital of the newly formed district. The district comprised of present-day districts of Erode, Tiruppur, Niligirs and parts of Karur, Palakkad in Kerala, Chamarajanagar in Karnataka. Nilgiris district was segregated in 1868. The region was hard hit during the Great Famine of 1876–78 resulting in nearly 200,000 famine related fatalities. The city experienced an earthquake with a magnitude of 6.0 on the Richter scale on February 8, 1900. The first three decades of the 20th century saw nearly 20,000 plague-related deaths and an acute water shortage.
The district experienced an economical boom in the 1920s and 1930s due to the decline of the cotton industry in Mumbai. The region played a significant role in the Indian independence movement. Post independence, the district has seen rapid growth due to industrialisation.
In 1927, Karur was separated from the district and merged with Tiruchirapalli district. In 1956, Kollegal taluk was transferred to Mysore State. In 1979, Periyar district (Erode district) was formed after bifurication of six taluks of Bhavani, Gobichettipalayam, Sathyamangalam, Erode, Perundurai and Dharapuram. Further, Tiruppur district was formed in 2012 comprising parts of Erode district and Coimbatore district.