Ladd became known as a scream queen, having appeared in several successful horror films, including Cabin Fever (2002), Club Dread (2004), Death Proof (2007), and Grace (2009).

In 1994, she guest-starred in an episode of the NBC series Saved by the Bell: The New Class and made her big screen debut with a supporting appearance as a promiscuous college student opposite Alyssa Milano in the film Embrace of the Vampire.

In 1999, she appeared in Taking the Plunge, and also landed her first high-profile role alongside Drew Barrymore as a popular student who tortures an insecure copy editor in the teen comedy Never Been Kissed.

Ladd appeared in The Specials (2000), a comedy about a group of superheroes on their day off; in the film she played a neurotic named Nightbird.

Ladd starred as a college graduate and the victim to a flesh-eating virus in the horror film Cabin Fever (2002), Eli Roth's directorial debut.

[16] Quentin Tarantino cast her as a wild, partying Texan and the victim of a killer stuntman in Death Proof, his high-speed segment of the double–feature exploitation horror Grindhouse (2007),[17] alongside Rosario Dawson, Tracie Thoms, Zoë Bell, and Kurt Russell.

In her next film, the horror Grace (2009), Ladd portrayed a woman, who after a car accident, decides to carry her unborn baby to term anyway.

[22][23] John Anderson of Variety felt that Ladd played her role with "tongue planted firmly in cheek", in what he described as "a satirical creepfest that mines modern motherhood for all its latent terrors".

In 2012, she also appeared in the direct-to-DVD disaster film Air Collision, as a flight attendant, and in the thriller Murder on the 13th Floor, as a wife who discovers her husband is having an affair with the live-in nanny and decides to seek revenge.

In 2016, she reunited with Fitzpatrick for the short thriller film Brentwood Strangler, in which she played a lonely woman goes on a blind date with a man who, unbeknownst to her, was replaced by an active and notorious serial killer, opposite Adam J. Yeend and Annika Marks.

[30] In 2017, Ladd starred in the made-for-television thriller Stage Fright, as an opera soprano facing a series of dangers, and in the independent drama Blue Line, as a woman who, along with her best friend, go on a crime spree to rob her abusive husband and escape her marriage.