In 1861, at the age of 24, to the dismay of his parents, he departed from his first job as a clerk for the Great Northern Railway to pursue a career in art. He began exhibiting in 1862, under the patronage of the Leeds Philosophical and Literary Society, with paintings mainly of dead birds, fruit and blossom. He became particularly successful in the 1870s and was able to afford to rent a second home in Scarborough, which also became a favourite subject.
Dulce Domum (1855), on whose reverse Grimshaw wrote, 'mostly painted under great difficulties,' captures the music portrayed in the piano player, entices the eye to meander through the richly decorated room, and to consider the still and silent young lady who is meanwhile listening.
On Hampstead Hill is considered one of Grimshaw's finest, exemplifying his skill with a variety of light sources, in capturing the mood of the passing of twilight into the onset of night. In his later career this use of twilight, and urban scenes under yellow light were highly popular, especially with his middle-class patrons. .
His later work included imagined scenes from the Greek and Roman empires, and he also painted literary subjects from Longfellow and Tennyson. His reputation rested, and his legacy is probably based on, his townscapes. .
His early paintings were signed JAG, J. A. Grimshaw, or John Atkinson Grimshaw, but he finally settled on Atkinson Grimshaw.