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.When Boothby was six he travelled to England with his mother, and thus was educated at Salisbury, Lord Weymouth's Grammar (now Warminster School) and Christ's Hospital, London.

He returned to his native country at the age of 16, in 1883 .His grandfather had been a high court judge in his home state, and his father was a local politician; these connections doubtless led to his accepting a role as private secretary to the mayor of Adelaide, Lewis Cohen, but was "not contented" with the work.

In 1890, aged 23, 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. There was little opportunity for Boothby to progress in the Adelaide Corporation: thus, with the support of Cohen, Boothby moved to Brisbane where he believed that he would find "a wider opening for his talents". Perhaps wanting to get to know the country of his birth better, he went on a trek across the continent from North to South, later writing up his adventures in his first book, On the Wallaby (1894)

From Brisbane, Boothby, still in his early twenties, made his way to England, arriving in London (at the age of 27) in 1894. He now remained in England and 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. He wrote over 50 books over the course of a decade.