Ponzio was born in New York City and graduated from Georgia State University. As of the late 1990s, Ponzio began appearing in supporting guest roles on television series, including Dawson's Creek, One Tree Hill, Surface, Drop Dead Diva, CSI: Crime Scene Investigation, The Gates, NCIS, The Following and Banshee. She also appeared in films The Greenskeeper (2002), Road Trip: Beer Pong (2009), Life as We Know It (2010) and Upside (2010). Ponzio is known for her recurring roles as Angie on the Lifetime Television drama series Army Wives (2007–2009), and as Melissa McCall in the MTV teen drama Teen Wolf (2011–present). In 2013, she has a recurring role as Karen in the AMC drama series The Walking Dead.