He is best known for his romanticising depictions of rural scenes, and for creating Mulready stationery letter sheets, issued at the same time as the Penny Black postage stamp.

Early in his life, in 1792, the family moved to London, where he was able to get an education and was taught painting well enough so that he was accepted at the Royal Academy School at the age of fourteen.

His relationship with his wife however deteriorated gradually over the years, which is detailed in papers stored at the library of the Victoria and Albert Museum.

In a letter to him in 1827 she blamed him entirely for the collapse of their marriage, suggesting cruelty, pederastic activities and adultery were the reasons,[2][3] writing that one of his pupils, Harriet Gouldsmith, had told her Malready "preferred her little finger" to his wife and children, and accusing him having "had taken a low boy to your bed, and turned one adrift at midnight, to seek one at the house of an unmarried man".

Many of his early pictures show landscapes, before he started to build a reputation as a genre painter from 1808 on, painting mostly everyday scenes from rural life.

He also illustrated children's books including the first edition of Charles and Mary Lamb's Tales from Shakespeare in 1807;[7] William Roscoe's entertaining poem The Butterfly's Ball, and the Grasshopper's Feast in the same year; and a sequel to the latter by Catherine Ann Dorset.

His first painting of importance, Returning from the Ale House, now in the Tate Gallery, London, under the title Fair Time, appeared in 1809.