Caravaggio is a TV mini-series based on the life of the Italian painter Michelangelo Merisi da Caravaggio. It opens in 1577 when the painter was 5 years old. The plague had just hit and people who were still alive were burning their household possessions.

Some years have passed, and Michele's widowed mother has had some difficult decisions to make regarding her children. One of these is to send 12-year-old Michele to Milan to be an apprentice at the workshop of the well-known artist, Simone Peterzano. Michele has no desire to leave home and family.

Michele has a rough time of it in Master Simone's workshop. It's clear, however, that he has talent. A Knight of Malta comes into the workshop to have a look.

Michele manages to find a home for his painting, and receives something in exchange. Still at Maestro Simone's workshop, he grows up into a man and ends up trying to defend a young apprentice from being abused as he had been.

Michele goes back home after his mother dies and there, he spends some time with his childhood friend, Costanza Colonna. He tells her about his plans to go to Rome, the artistic center of the universe.

Once in Rome, Caravaggio looks for work in the studios of 2 Italian painters who were well-known at the time. Nobody seems very interested in his work.

Caravaggio falls ill and makes the acquaintance of Mario Minniti who becomes a friend to him. He takes him to the hospital of the church of Santa Maria della Consolazione in Rome.

Caravaggio meets Onorio Longhi, Italian architect and poet, and a bit of a bohemian. Longhi takes him to meet his friend Cesare D'Arpino, who is looking for assistants in his workshop.

After a night of drinking and brawling, Michele is finishing a painting outside the workshop. Baron Cenci shows up and likes what he sees on the easel. The Baron's daughter is in the carriage and exchanges a few words with Michele.

Michele gives one of his works to the girl in the carriage. She is Beatrice Cenci and is chained to her seat. Later, Michele is seriously wounded while loading a piece of art onto a horse-drawn cart.

Caravaggio manages to sell one of his paintings and decides to leave d'Arpino's workshop. His friend finds him a room, and he starts working on a painting, now known as"Boy bitten by a lizard".

Prosperino tries to sell Michele's painting of the "boy bitten by a lizard," and attempts to be professional. The three friends get their hopes up, but soon have to face reality. Michele and Mario quickly lose their patience and become belligerent.

Michele and Mario are having a hard time. But Michele can't bring himself to paint things he doesn't believe in, even at the risk of going hungry.

Word seems to be getting around that Merisi is a very talented painter. In bed with malaria, Michele himself is the last one to hear about it.

Young Michele thus enters into the service of Cardinal Francesco Maria del Monte, man of culture and art connoisseur. All he has to do is what he does best: paint.