A prominent scream queen, she is known for her roles in horror films, as well as projects of other genres in both Australia and the United States.

The following year, her performance as a depressed teenager in the drama film 2:37 earned her acclaim and a nomination for the AACTA Award for Best Actress.

She would later gain further nominations in the category, for Mel Gibson's Hacksaw Ridge (2016), Berlin Syndrome (2017), and Ride Like a Girl (2019).

Palmer had early Hollywood roles in Bedtime Stories (2008), The Sorcerer's Apprentice (2010), Take Me Home Tonight (2011), and I Am Number Four (2011), to varied success.

Further recognition came for her starring roles in the horror films Warm Bodies (2013), Lights Out (2016), and The Twin (2022), establishing Palmer as a leading lady.

Expanding her ventures, Palmer co-wrote and co-produced the drama film The Ever After (2014), in which she also starred, alongside her husband Mark Webber.

[4][5] Palmer stated to Interview that she "came from rather humble beginnings";[6] she lived in public housing with her mother, while regularly visiting her father at his farm near Mylor in the Adelaide Hills (which she later purchased as an adult).

[9][10] Palmer was a student at Mercedes College, a private Catholic day school,[11] and won a local-casting audition, "Search for a Movie Star," in 2003.

[12] Her first acting job was dressing up as a Strawberry Shortcake doll and as an elf assistant to mall Santa Clauses on weekends for promotions in shopping centres near Adelaide.

[10] She was a fast-food attendant at Hungry Jack's in Rundle Mall in 2005, before working at clothing retailers Supré, Mambo Australia and Cotton On.

Palmer starred in the psychological thriller Restraint, with English actor Stephen Moyer and Calvin Klein model Travis Fimmel.

Shot on location around New South Wales in mid-2005, the film was written by Dave Warner and directed by David Denneen.

[31] Palmer was cast to star with Tom Sturridge in her first American feature, Jumper, a science fiction film directed by Doug Liman.

[10] She made her Hollywood feature film debut in The Grudge 2 in 2006, a horror sequel starring Amber Tamblyn and Sarah Michelle Gellar.

[34] In early 2007, Palmer was cast as Tori Frederking in the comedy Take Me Home Tonight, starring Anna Faris, Dan Fogler and Topher Grace.

[10] In November 2007, Palmer was cast as the villain, Talia al Ghul, in the DC Comics superhero film, Justice League: Mortal, alongside D.J.

George Miller was set to direct the film, but it was cancelled by Warner Bros. due to script rewrite issues and the 2007–2008 Writers Guild of America strike.

[16] She was picked that year by Adam Sandler from an audition tape to play his love interest in the Walt Disney Pictures children's film, Bedtime Stories.

[42] Palmer won the romantic lead in Disney's The Sorcerer's Apprentice, produced by Jerry Bruckheimer and directed by Jon Turteltaub.

The film was based on the relevant section of the animated film Fantasia (1940), which was set to a short symphonic poem for orchestra by Paul Dukas, L'apprenti sorcier (The Sorcerer's Apprentice, published in 1897, and by far, the best known of Dukas' compositions), all of which were inspired by the eponymous poem by Johann Wolfgang von Goethe.

[54] Palmer was going to star in Fury Road, a sequel to the Mad Max series by Australian filmmaker George Miller, but didn't join the cast due to scheduling conflicts.

[61] Palmer starred in the 2013 zombie film, Warm Bodies, produced by Summit Entertainment, and based on a young adult novel by Isaac Marion.

[66] Palmer then starred in Love and Honor with Liam Hemsworth, an independent romance filmed in mid-2011 in Ann Arbor, Michigan.

[70] In 2014, she co-starred alongside Josh Hartnett, Rosario Dawson and Penn Badgley in the romantic drama Parts per Billion.

[82] In October 2015, it was learned that Palmer would participate in a short film called Too Legit with Zoe Kravitz, Clark Gregg, Nate Corddry and Lauren Weedman.

[96] In 2018, Palmer began a starring role as Diana Bishop in the British supernatural drama series A Discovery of Witches.

[98] Palmer will star alongside Bella Heathcote and Philippa Northeast in the television adaptation of Sally Hepworth's novel The Family Next Door for the ABC.