Kernoff served as an apprentice cabinet maker with his father, and attended a London primary school.

His studio was based at Stamer Street, Dublin, from where he painted portraits of leading literary and theatre figures, including Brendan Behan, Hilton Edwards, F. R. Higgins, James Joyce, Flann O'Brien, Sean O'Casey, and W. B. Yeats.

He was the set designer for Sean O'Casey's The shadow of a gunman and Lord Dunsany's The glittering gate.

[3] Kernoff was a member of the Friends of Soviet Russia, with his woodcuts used to illustrate labour and republican newspapers throughout the 1930s and 1940s.

[4] He developed an interest in modernism and the avant-garde movement in the 1920s, but returned to realism for his works documenting social life in both rural and urban Irish settings.

He frequented the Palace Bar on Fleet Street, and would trawl Dublin pubs looking for more portrait subjects.

[4] Kernoff's work has been stylistically compared with L. S. Lowry, with John Ryan describing him as "our Boswell in paint".

[5][2] It has been suggested that Kernoff's painting, A Bird Never Flew on One Wing, was the inspiration for the ears of the character Spock in the original Star Trek television series.

The painting hung in O'Brien's pub, Leeson Street, where it is believed a Hollywood designer saw it, though this story may be apocryphal.