He first exhibited at the Free Society of Artists in 1761 and between 1762 until around 1764 he undertook various commissions between Oxford, the Midlands and London. These included the principal of Brasenose College, Oxford, Dr Francis Yarborough, the poet Anna Seward (National Portrait Gallery, London) as well as numerous portraits of the Legge family, commissioned by the second Earl of Dartmouth. He continued to exhibit with the Society of Artists up to 1776, when he then began exhibiting with the Royal Academy.
 
In 1768. he was granted permission by the East India Company to travel to Bengal, India, to work as as artist, becoming the first professional artist to make a career there. Arriving in Madras, among his first commissions was a portrait of Lord Pigot, the former Governor of Madras and his clientele consisted of nabobs, merchants and army officers. He also painted a group portrait of Muhammed Ali Khan, nawab of Arcot , with his five sons, which Kettle exhibited at the Society of Artists in 1771, as well as a full-length portrait of Muhammed. (Victoria and Albert Museum, London). 
 
By late 1771, kettle was in Calcutta where he painted a large double portrait of Charles and John Sealy (Courtauld, London) and Warren Hastings, whom Kettle painted at least three times. Whilst in Calcutta, he took an Indian 'bibi' or mistress, and had two daughters, Ann and Elizabeth. « Less