Born in Fusignano, an Italian village between Ravenna and Bologna, he studied in Bologna and in about 1685 settled in Rome, under the patronage of Cardinal Pietro Ottoboni, where he published his first violin sonatas. He was one of the first great violinst and his music, marked by graceful melody, includs a set of "concerti grossi" and five sets of chamber sonatas.

Corelli's personal life has been the subject of much speculation. Most scholars now believe him to have been discreetly homosexual. He never married and lived closely with male friends.

Corelli became utterly devoted to another of the cardinal's employees, the second violinist Matteo Fornari, whom he met in 1682. According to one source, the composer was never far from Matteo's side for close on twenty years after that first meeting. This long standing intimacy is alluded to in the two fine trio sonatas dedicated to Corelli and Fornari by the younger composer Guiseppe Valentini.

Corelli was admitted to the Academy in Rome in 1706. Two years later, he retired from public life. He died in 1713, a wealthy and widely respected man. He was buried in the Pantheon, next to the painter Raphael. Fornari oversaw the publication of Corelli's Opus VI concertos after Corelli's death.