On television, she played Quinn James in the CW teen drama series One Tree Hill;[2] recurred as Becca Butcher in the Amazon Prime Original The Boys; and starred as Julie Swagger, the wife of lead character Bob Lee Swagger on the USA Network series Shooter.

In 2009, VanSanten appeared as Lori Milligan in The Final Destination, the fourth installment of the eponymous horror film franchise.

In spring 2012, VanSanten shot Golden Christmas 3—a family-oriented holiday romantic comedy directed by Michael Feifer—opposite Rob Mayes, Mark Famiglietti, Nikki DeLoach and Orson Bean.

VanSanten portrayed Patty Spivot in the second season of The CW Arrowverse TV series The Flash, based on the DC Comics character of the same name.

She was Detective Joe West's (Jesse L. Martin) new protégée, the only member of his new metahuman task force at the Central City Police Department besides Cisco Ramon (Carlos Valdes), and a brief love interest of Barry Allen (Grant Gustin).

[12] From 2019 to 2023, VanSanten has starred as Karen Baldwin in the Apple TV+ original science fiction space drama series For All Mankind.