Siffredi was born in Ortona, Abruzzo.

After starting his film career in France, he subsequently starred in films abroad in such varied locales as Budapest, Hungary (which later became the headquarters of his production company, Rocco Siffredi Produzioni), Canada, Russia, Brazil, and various Eastern European countries. He became famous in the pornographic film community for his penchant for anal sex and analingus, which built him a cult following over the course of his career.

Siffredi's films vary widely in content and tone. He has appeared in romantic adventures and comedies in the Vivid style, but his later work with John Stagliano's Evil Angel Video involve BDSM scenes in which Siffredi spits on women, slaps them, performs irrumatio and watersports (censored in U.S. versions), makes his co-stars gag during deepthroat, and occasionally pulls hair to the point of causing tears. On rare occasion, Siffredi himself has been the recipient of dominant sexual treatment, portraying the submissive in films like Rocco più che mai a Londra 2, Animal Trainer 11, and Il Marchese de Sade, appearing in drag in the latter.

Many of his films begin with affectionate, romantic scenes that turn into bouts of marathon violent anal sex. Climaxes often involve such activities as Siffredi focusing the camera on the distended anus of one of his female co-stars, spitting into it, ejaculating into it, and then having other co-stars clean the woman's anus with their tongues.

He has also produced and starred in "shemale" movies.

Siffredi took this tradition one step further when directing Never Say Never to Rocco Siffredi, when, filming in a park, Siffredi grabbed passing (presumed) strangers and then requested that his female co-stars perform oral sex on them. Although they appear genuine, it is not uncommon for such seemingly realistic scenes to be set up ahead of time by directors/producers. Despite the sometimes extreme nature of his genre of pornography, he has been consistently able to find young European actresses willing to star in his pictures.