Wersching began her acting career with a guest appearance on the show Star Trek: Enterprise, and moved on to guest starring roles on such shows as Charmed, Killer Instinct, Supernatural and Cold Case. From March to November 2007, she played the recurring role of Amelia Joffe on the ABC Daytime soap opera General Hospital. She has also worked in theaters such as Victory Gardens, Marriott Lincolnshire, and the Utah Shakespearean Festival.
Wersching played FBI Special Agent Renee Walker in Seasons 7 and 8 of 24.
After her two season stint in 24, Wersching guest starred on various shows, including CSI, NCIS, Rizzoli & Isles, Hawaii Five-0, Body of Proof, Dallas, Revolution, Castle, Blue Bloods, The Vampire Diaries and Touch (which stars her 24 co-star Kiefer Sutherland). In 2014, she was a series regular for the first season of the Amazon Prime crime show Bosch.
Wersching played catcher for the National League in the 2009 Taco Bell All-Star Legends and Celebrity Softball Game.
In December 2012, it was revealed that in the PlayStation 3 exclusive The Last of Us Wersching was the voice and mo-cap actor of the character Tess. Her character was teased on Geoff Keighley's Twitter account before finally revealing her in the story trailer shown on Spike Video Game Awards on December 7, 2012.