He was born in Kensington, London, to Augusta Amherst Austen, an organist and composer, and Thomas Anstey Guthrie.

[3][4] The popular success of his story Vice Versa (1882) with its topsy turvy substitution of a father for his schoolboy son, at once made his reputation as a humorist of an original type.

[2] Guthrie became an important member of the staff of Punch magazine, in which his voces populi and his humorous parodies of a reciter's stock-piece (Burglar Bill, &c.) represent his best work.

In 1903, his successful farce The Man from Blankley's based on a story that originally appeared in Punch, was first produced by Sir Charles Hawtrey at the Prince of Wales Theatre, in London.

Vice Versa was adapted as a play in 1883 and has been filmed many times, usually transposed in setting and without any credit to the original book.