Sorrentino's first film as screenwriter, Polvere di Napoli, was released in 1998. He began directing several short movies, like L'amore non ha confini, in 1998, and La notte lunga, in 2001. His debut with a long feature is One Man Up (L'uomo in più), awarded with the Nastro D'Argento for the best young director.
Sorrentino's next feature, The Family Friend (L'amico di famiglia), was shown at the Cannes Film Festival in May and the London Film Festival in October 2006. It tells the story of a malicious septuagenarian loan-shark who develops a fixation with the beautiful daughter of one of his customers. Sorrentino made his acting debut with a cameo appearance in Nanni Moretti's film The Caiman (Il caimano), which was also shown at the 2006 London Film Festival.
Sorrentino's following film, Il Divo, is a dramatised biopic of Giulio Andreotti, the controversial Italian politician. The feature, which won the Prix du Jury at Cannes Film Festival, sees Sorrentino reunited with The Consequences of Love star, Toni Servillo, who plays the part of Andreotti.
As of January 2009, Sorrentino was working on the screenplay for a film version of Niccolò Ammaniti's Ti prendo e ti porto via (Steal You Away).
This Must Be the Place marked the English-language feature debut of the Italian filmmaker. The plot centres around a middle-aged wealthy rock star, played by two time academy award winner Sean Penn, who becomes bored in his retirement and takes on the quest of finding the guard of the German camp where his father was imprisoned, who now lives in hiding in the U.S. The film was co-written by Sorrentino and Umberto Contarello and premiered in competition at the 2011 Cannes Film Festival.