In 1746 he married and in 1749 Gainsborough left London and returned to Sudbury. As it proved difficult to make a living as a painter in Sudbury, he decided to move to the fashionable city of Bath in 1759, with two young daughters in tow. This move gave him more opportunity to sell and take commissions for portraits. He developed a naturalistic approach to portraiture by abandoning 'conversation pieces' and painting a number of straightforward head-and-shoulder portraits.

Under the influence of van Dyck, Rubens and Claude his style developed rapidly and by 1761 he was contributing exceptional work to the annual Society of Artists exhibitions in London. Gainsborough was also a founding member of the Royal Academy of Arts in London, which was lead by Joshua Reynolds. At the Academy's first public exhibition in 1768, Gainsborough showed a portrait of Isabella Lady Molyneux. Uniquely known to catch a good likeness, he gradually assimilated this quality with the grandeur of van Dyck and by the time he showed his work at the inaugural exhibition of the Royal Academy in 1769 his skill was unassailable.

In 1774, perhaps because he declined to exhibit at the Academy, he moved to London. At Schomberg House in Pall Mall he built a studio in the garden and he continued to attract a wide clientele. Three years later he began to work for the Royal family, which prompted him to exhibit at the Academy once more.

In 1784 he finally broke with the Academy after they refused to hang another Royal portrait as he wished. Instead he began to hold annual exhibitions of his work at Schomberg House.

Gainsborough did not paint his portraits in a studio, but against a backdrop of a landscape, trying to depict the sensitive and the casual nature of an otherwise artificial and stiff process Gainsborough's art was influenced among others by the Venetian and Dutch style of painting.

He contracted cancer and died on 2 August 1788. Reputedly his last words were: 'We are all going to Heaven, and Van Dyke is of the company'.