After organ studies at the Conservatorio della Pietà dei Turchinihe spent eight years serving as the institution's organist. in 1703 while Alessandro Scarlatti was on an extended leave of absence from his position as musical director at the Neapolitan court Mancini made an unsuccessful bid to replace him. A year later after Scarlatti, still missing from court, had his position officially declared vacant, Mancini again failed to secure for himself either the top position or that of assistant, having to settle for the job of first court organist. By the time of the Spanish-Austrian War of succession in 1707 he tried to use political intrigue to advance his cause. He met the Austrian Count Dann with a group of musicians and a specially composed Te deum to celebrate the Austrian victory. He did manage to get the covered court appointment, but his triumph was premature. In a year Scarlatti was recalled from Rome to resume his duties, forcing Mancini to wait until his death in late 1725 to be definitively named musical director, By this time his most active years as a composer had passed. He died seven years later.
Mancini is typically Neapolitan. His concertos are imbued with the kind of pungent harmonic shifts which made early eighteenth-century Neapolitan opera sound so dramatic.