Tilly Kettle was born in London, the son of a house painter. He received his early training from his father, studied in the Duke of Richmond’s gallery of casts and at the Academy in St Martin’s Lane. He exhibited portraits at the Society of Artists, of which he became a Fellow. He was in practice as a portrait painter in London from 1764 until 1769. In 1770 he left for India, where he remained for seven years. There he amassed a considerable fortune painting portraits of nabobs and native princes; he sent home a number of pictures for exhibition.
Kettle returned to England in 1777, married, and built a house for himself in Old Bond Street, opposite Burlington Gardens. He also at that time exhibited pictures at the newly formed Royal Academy. Unfortunately he over-stretched himself, became bankrupt and was obliged to retire to Dublin. In 1786 he set off again, at the age of 52, overland to India, hoping to repair his fortunes, but he fell ill near Aleppo, where he died.