Paul Attanasio was born in The Bronx, New York City, the son of Connie, a real estate broker, and Joseph Attanasio, a commercial consultant. He grew up in the Pelham Bay section of the Bronx, and later in Tenafly, New Jersey, where he attended public high school. He is a 1981 graduate of Harvard College, where he lived in Currier House, and earned his law degree at Harvard Law School in 1984.

In 1995 he won a BAFTA for his screenplay adaptation for the drama Quiz Show. He later wrote the screenplays for the thriller Disclosure, the gangster movie Donnie Brasco, the science fiction film Sphere, and the political thriller The Sum of All Fears. In 2000 he returned to television and started executive producing, in addition to writing, the medical drama Gideon’s Crossing and the pilot for R.U.S.H. Along with David Shore, he is one of the creators of the TV series House, of which he was executive producer. In 2006 he wrote the screenplay for the dramatic film The Good German. In 2017, it was confirmed that Attanasio will be the writer and executive producer on the new Amazon Video series Tong Wars. He is a co-creator of the series Bull (2016 TV series). He is the writer/producer of the 2020 CBS police drama Tommy.