Applegate was raised in Moon Township, Pennsylvania, a suburb of Pittsburgh, in an Irish American Catholic family.
In 1987, Applegate appeared in a television version of the Mercer Mayer children's book There's a Nightmare in My Closet, also as the main character's mother.
In the early 1990s, Applegate was a host of Close Up on C-SPAN, a weekly public affairs program that featured a high school student audience.
She anchored the Fox 25 Morning News for about a year from September 2003, then moved to New York sister station WNYW in October 2004.
Applegate joined WNYW as co-anchor of the station's morning program, Good Day New York, in 2005.
Applegate also guest-hosted radio talk shows hosted by Joan Hamburg on WOR in New York, and Howie Carr on WRKO in Boston.
With three months remaining in her one-year contract, she was allowed to leave News 12 in order to join WPIX.
The Tribune Company-owned station named her as sole anchor of its revamped 10:00 PM newscasts on weeknights; she started in that capacity on October 11, 2010.