Ferrara entered the adult industry in 1997 after winning a competition. He works in both European and American films and is one of the more popular uncircumcised actors appearing in American pornography. He was originally a protégé of Rocco Siffredi, and had an award winning acting career, making his American acting debut in John Stagliano’s Fashionistas. In 2002 he appeared in Snoop Dogg's Hustlaz: Diary of a Pimp. In 2003 he started directing gonzo pornography for Platinum X Pictures, a subsidiary of Red Light District Video. In 2004 he began directing for Red Light. He appeared with Stefani Morgan in Sunny, her first film for Vivid Entertainment in 2005.

After working for Red Light District for 2 years he began directing for Evil Angel in May 2006. His first EA film was Evilution, starring Naomi, Melissa Lauren and featuring the comeback of Nici Sterling. Since then he has directed series including Fucked On Sight, Slutty & Sluttier, Raw, Evil Anal, Battle of the Sluts, Anal Expedition, Teen Cum Squad, Bangin' Black Boxes, Ass Attack, I'm Your Slut, Mindfuck, and New Whores On The Block.

In 2005 Manuel Ferrara married to retired porn star actress Dana Vespoli.

On January 9, 2010 he became the second actor to win AVN's Male Performer of the Year 3 times.