Boothby was born in Adelaide, son of Thomas Wilde Boothby, who for a time was a member of the South Australian Legislative Assembly. Guy Boothby's grandfather was Benjamin Boothby (1803-1868), judge of the supreme court of South Australia from 1853 to 1867. Guy Boothby was educated at Salisbury, near Adelaide, Lord Weymouth's Grammar (now Warminster School) and Christ's Hospital, London.
In 1890 Boothby wrote the libretto for a comic opera, Sylvia, which was published and produced at Adelaide in December 1890, and in 1891 appeared The Jonquil: an Opera. The music in each case was written by Cecil James Sharp.
Boothby worked as secretary to the mayor of Adelaide. In 1894 he published On the Wallaby or Through the East and Across Australia, an account of the travels of himself and his brother, including a description of their journey across Australia from Cooktown to Adelaide. In the same year his first novel, In Strange Company, was published in London and was quickly successful. Boothby moved to the United Kingdom in 1894. He wrote over 50 books over the course of a decade, before dying of pneumonia in Bournemouth.
Some of Boothby's earlier works relate to stories of Australian life, but later he turned to genre fiction. He was once well known for his series of five novels about Doctor Nikola, an occultist anti-hero seeking immortality and world domination. In A Prince of Swindlers he created the character of Simon Carne, a gentleman thief in the Raffles mould: Carne first appeared in Pearson's Magazine in 1897, predating Raffles by two years.
