In spring 1584 he starts an apprenticeship period at painter Simone Peterzani’s shop, a "latemannerist" who frescoed the Certosa di Garegnano in Milan, where he works for four years.

In 1592 he moves to Rome where he is the guest of monsignor Pandolfo Pucci from Recanati and for a few months he works in the shop of Giuseppe Cesari, called "il Cavalier d'Arpino".

In Rome, Caravaggio paints some of his most significant works: "Ragazzo con il canestro di frutta" and "La buona ventura" (1594),  "San Francesco in estasi", "Riposo nella fuga in Egitto", "La Maddalena penitente" (1595), "Bacco", "Suonatore di liuto con vaso di fiori e frutti", "Il canestro di frutta" (1596), in 1597 he paints "Medusa" currently on display at the Uffizi Gallery in Florence.

In those years he obtains his first commission: San Matteo’s stories for the Contarelli chapel in the Church San Luigi dei Francesi , later he is asked two paintings: "Crocifissione di San Pietro" and "Conversione di San Paolo", both for the Cerasi chapel in the Church Santa Maria del Popolo.

In 1601 he paints one of his greater masterpieces "Cena in Emmaus" , on display at London’s National Gallery. 1600 marks the beginning of trouble with the law for Michelangelo Merisi because of his hot temperament which leads him to get involved in brawls and fights.

In 1603 he is arrested and tried for defamation, with friends, of painter Giovanni Baglione  - he obtained probation owing to the intervention of the ambassador to the King of France -, later he is arrested for illegal possession of firearms, he injures notary Pasqualone and runs to Genova where he finishes "Ecce Homo".

He returns to Rome and, in May 1606, kills, during a brawl, Ranuccio Tomassoni da Terni. This murder brings him to "capital banishment" (anybody can carry out the death sentence) so he finds refuge with some of his protectors and then reaches Naples where he paints the altar-piece depicting the "sette opere della Misericordia" for Pio Monte della Misericordia.

He leaves the Parthenopean city, spending three years in constant fleeing, goes to Malta from which he is expelled, moves to Siracusa, to Messina – where he paints "Resurrezione di Lazzaro"- , to Palermo and finally returns to Naples.

In 1610 he obtains grace form the Pope and while he tries to finally return to Rome, he dies in circumstances that never became clear on a beach near Porto Ercole.