Cruikshank was born in London. His father, Isaac Cruikshank, was one of the leading caricaturists of the late 1790s and Cruikshank started his career as his father’s apprentice and assistant.
His older brother, Isaac Robert, also followed in the family business as a caricaturist and illustrator. Cruikshank’s early work was caricature; but in 1823, at the age of 31, he started to focus on book illustration. He illustrated the first, 1823 English translation (by Edgar Taylor and David Jardine) of Grimms’ Fairy Tales, published in two volumes as German Popular Stories.
On 16 October 1827, he married Mary Ann Walker (1807–1849). Two years after her death, on 7 March 1851, he married Eliza Widdison. The two lived at 263 Hampstead Road, North London.
Upon his death, it was discovered that Cruikshank had fathered 11 illegitimate children with a mistress named Adelaide Attree, his former servant, who lived close to where he lived with his wife. Adelaide was ostensibly married and had taken the married surname ‘Archibold’.