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.

[2] She also appeared in films The Greenskeeper (2002), Road Trip: Beer Pong (2009), Life as We Know It (2010) and Upside (2010).

[citation needed] 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 (2011–2017).

[3] In 2013, she had a recurring role as Karen in the AMC drama series The Walking Dead.

The majority of the original cast members, including Ponzio, were set to reprise their roles.