Leigh began by painting miniatures, and by 1796 she was exhibiting at the Royal Academy.

[2] She created notable full-sized illustrations for Curtis's Botanical Magazine as well as for his other works, Monograph on the Genus Camellia (1819) and The Beauties of Flora .

[3] She was supported in her work by the architect Sir John Soane, who commissioned the watercolour The Flowers of Shakespeare (1835), which depicts a bust of the bard in Soane's collection surrounded by all the flowers mentioned in Shakespeare's works.

In 1807, Leigh married the actor and painter Alexander Pope, becoming his third wife.

She taught painting, and her students included Princess Sophia of Gloucester and other members of the British aristocracy.