She was born to Italian-Irish father Vince Minnillo and Filipina mother Helen Berecero. As a child, her family moved numerous times due to her father's work in the United States Air Force. Her family spent time in California, Nevada, Florida, Germany, and Japan before eventually settling in Charleston, South Carolina. Minnillo became Miss South Carolina Teen USA 1998, and went on to win the 1998 Miss Teen USA Pageant.

Minnillo has hosted TRL on MTV since 2003. In 2005, she also became a New York-based reporter for the entertainment news show, Entertainment Tonight. Before joining MTV, she had minor roles in the television series City Guys, That's Life, and Maybe It's Me. In 2003 Minnillo served as a celebrity judge for the Miss Teen USA pageant. In addition to her work on TRL, she has served as a host or co-host for a variety of MTV specials.

In May 2006, Maxim magazine listed Minnillo as #15 in their Hot 100 issue. She was listed as #62 in the 2005 issue.

Minnillo is currently dating singer Nick Lachey. She had previously been involved with professional baseball player Derek Jeter.