Born in Marino near Rome, Italy. Of his early life almost nothing is known, nor of his early musical training. His first known appointments were at Tivoli Cathedral where he was a singer in 1623 and an organist from 1624. In 1628 he moved first to Assisi then in 1629 to the Collegium Germanicum et Hungaricum (the German College of the Jesuits) in Rome as maestro di cappella (chapel master). The German College was a prestigious appointment - Victoria had been one of the previous incumbents. In 1637, he was ordained as a priest. . His responsibilities included training the choirs and providing liturgical music for the church of Sant'Apollinare. His salary was low but he made money by teaching aristocratic pupils including Marc-Antoine Charpentier, Johann Kaspar Kerll and Christoph Bemhard. That he was in a comfortable situation, both financially and professionally, is suggested by his rejection of the post at St. Mark's in Venice on Monteverdi 's death in 1643 and the position of maestro for the emperor's son, Leopold Wilhelm of Brussels.In 1656, Queen Christina of Sweden made Carissimi her Maestro di Cappella del concerto di camera. Carissimi is also known to have worked at the Oratorio del Santissimo Craciffiso. He remained in Rome until his death.

Carissimi's position in the history of church, vocal and chamber music is somewhat similar to that of Francesco Cavalli in the history of opera. Carissimi was the composer who first made the chamber cantata the vehicle for the most intellectual style of chamber music. Carissimi is also noted as one of the first composers of oratorios - so called from their performance at Oratorio del Santissimo Craciffiso. His oratorios are notable for their clear text settings, the importance given to the chorus, and the use of expressive gestures to intensify and illustrate meanings in the text. Carissimi's oratorios are serious sacred pieces, He may also be credited for having given greater variety and interest to the instrumental accompaniments of vocal compositions. Carissimi also met with fame as a composer of cantatas, and, as with the oratorio, he advanced that genre substantially.

He was a major influence on the next generation both through his pupils but also through his influence on such as Alessandro Scarlatti.