The Italian beat off competition from four other nominees, including the French film Blue Is the Warmest Color (La Vie d'Adèle) and Japan's The Wind Rises (Kaze Tachinu).
Collecting the award along with producer Nicola Giuliano, Sorrentino thanked the “crazy country, but beautiful” Italy.
The Great Beauty, which follows a journalist’s life in Rome, has already won a string of accolades including four European Film Awards.
Sorrentino’s film has also been nominated for a BAFTA award in the UK and is shortlisted for the Oscars in March.
Watch a video of Sorrentino's acceptance speech: