Graduating with a bachelor of arts in journalism from New York University, Debbie has been a talk-show host, panelist, actress and producer for more than ten years. She began her career at MTV, working on numerous specials, news pieces, a show called Unfiltered and the Video Music Awards. In 1997, she landed a coveted cohost position on Barbara Walters' talk show The View, along with Meredith Vieira, Star Jones and Joy Behar.

Matenopoulos left The View in 1999 to join the TV Guide Channel, where she hosted the sports show The Moves, the movie show The Screening Room and the entertainment show Entertainment News. She also hosted a 2003 Emmy special and was a presenter at the First Annual TV Guide Awards. Throughout her time at the TV Guide Channel, Matenopoulos interviewed all of the top stars of the day and was also the cohost of the hit daytime show Good Day Live from 2004-2005.

Matenopoulos' fame has allowed her to become a personality in niche markets, as well. Her role as a celebrity reporter, Claymation version of herself on MTV's Celebrity Deathmatch led to her becoming mistress of ceremonies for the videogame adaptation on PlayStation 2. She served as TiVo's guide girl, played a singer on NBC's American Dreams and starred in the award-winning short film The Sopranowitzes in 2001.

Most recently, fans of Debbie saw her warm up the red carpet and celebrities galore on E!'s Live Countdown of the Academy Awards and Live from the Red Carpet Golden Globes show.