Very little is known about Locatelli's early life and training, other than that he held a post as violinist in Bergamo until 1711. By 1712, he was in Rome, probably studying with Giuseppe Valentini, Corelli's rival. During the subsequent years, Locatelli worked exclusively as a violinist, particularly at the basilica of St. Lorenza in Damaso, Italy. In 1725, he was appointed virtuoso da camera of Mantua, a position which allowed him free rein to travel as a virtuoso.
In 1729, Locatelli moved permanently to Amsterdam, where he devoted his attention to teaching and composing with an occasional concert tour. He was also involved in importing Roman violin strings and in publishing. By his death in 1764, Locatelli had been successful enough to leave behind a considerable estate, as well as a compositional legacy that remained fairly current until the beginning of the next century.