Of Sicilian descent, Cortese was born in Sewickley, Pennsylvania, and graduated from Quaker Valley High School in Leetsdale, where he played football and basketball. Prior to becoming an actor, Cortese played college football as a walk-on at the University of North Carolina as a backup quarterback. In his freshman year in 1986, the Tar Heels went to the Aloha Bowl in Hawaii. Cortese never played a down and graduated from UNC with a B.A. in broadcasting.
During Burger King's "Your Way, Right Away" advertising campaign during the 1990s, Cortese was hired as the fast-food company's official spokesperson.
Cortese first came to prominence as team coach of The Bricklayers on MTV Rock N' Jock and host of MTV Sports from 1992 to 1997. In 1994, he co-starred on the short-lived CBS police drama Traps with George C. Scott. He gained further recognition in 1995 as Jess Hanson in Melrose Place. He played Jake Hanson's half brother for 8 episodes in the third season but was killed off in that season's finale. He had the main role as Jason in the 1996 movie The Lottery. He had starring roles in the 1993 remake/sequel of Route 66, Traps, The Single Guy, Veronica's Closet, Rock Me Baby and Ball & Chain.
Cortese appeared in the NBC television series Seinfeld, where he played Tony, Elaine's ultra-cool, vapid, good-looking boyfriend. In the episode, titled "The Stall", he was dubbed a "mimbo" (a male bimbo). He was also featured in The WB television series What I Like About You in a recurring role as Vic, Val's boss, from 2002 to 2003 a role he reprised as a series regular from 2005 to 2006 during the fourth and final season, which he directed one episode and in two episodes of 8 Simple Rules in 2004, playing Bridget's tennis coach. He has also starred in the natural horror film Locusts: The 8th Plague.
In 2008, Cortese landed a role in Soccer Mom as a famous Italian soccer player alongside Emily Osment.
In 2013, Cortese serves as the host of truTV's Guinness World Records Unleashed. The series debuted on February 7, 2013.
On October 11, 2014, while reprising his role as Stefon on Saturday Night Live, Bill Hader continually mentions Dan Cortese's name during the show's Weekend Update segment when he speaks of New York City's hot spots.
