Sabatini was born in 1875 in the small town of Jesi, Italy. His English mother and Italian father were both well-known opera singers. They traveled extensively so they sent their infant to live in England until he was seven. Rafael then lived in Portugal and Milan with his parents until he was sent to school in Switzerland. He was a voracious reader and was proficient in four languages. At age seventeen his father sent him to Liverpool to work as a translator.

He began writing romances at the age of twenty and his short fiction was published in national magazines. In 1905, he quit his translator job to devote himself to writing full time, producing a book a year. That same year he married a daughter of a well-to-do Liverpool paper merchant and four years later they had a son, Rafael-Angelo. Sabatini became a British citizen during WWI and worked in the British Intelligence as a translator. In the 1920's, with the publication of two international best-sellers, Scaramouch and Captain Blood, he became an overnight success.

In 1927, Rafael was devastated by the death of their only child, who was killed in an automobile accident. He fell into a deep depression, wrote very little, divorced his wife and suffered financially from The Great Depression. However, life improved when he moved outside London to Wye in 1931, and remarried at age 60. In his later years he spent his time writing, fishing and skiing in Switzerland, where he died in 1950.