That same year, she made her film debut in The Adventures of Sharkboy and Lavagirl in 3-D as Marissa, the Ice Princess, and also appeared as Millie Rose for two episodes of the short-lived TNT series Wanted, alongside her former Family Affair co-star, Gary Cole.

[citation needed] Pieterse appeared in the 2007 film Good Luck Chuck, playing a young goth girl who places a curse on the titular character.

She played the younger version of Sarah Michelle Gellar's character in the 2007 film The Air I Breathe, along with such co-stars as Kevin Bacon, Forest Whitaker, and Emile Hirsch.

[citation needed] Pieterse was 13 years old in late 2009, when she was cast in the Freeform teen drama television series Pretty Little Liars (2010–2017) as Alison DiLaurentis, the former "queen bee" of her high school clique.

In 2011, she appeared as Amy Loubalu in the Disney Channel Original Movie Geek Charming, and also as a teenage girl in the film X-Men: First Class.

Pieterse played Japonica Fenway, a young lady involved with cocaine, in the film Inherent Vice (2014), based on the novel of the same name by Thomas Pynchon.

[25] On August 16, 2021, Deadline announced that Pieterse had been cast in Netflix's film adaptation of Annie Barrows’ New York Times bestselling book series Ivy + Bean alongside Jesse Tyler Ferguson, Jane Lynch and Nia Vardalos.

[26] In July 2023, Deadline reported that Pieterse had been cast in psychological thriller film The Image of You (2024), starring in a dual roles of twin sisters of Anna and Zoe.

[30][31] On December 10, 2013, she released her fourth single "No", an upbeat track about "standing strong in your convictions" and saying no when an unfaithful, lying ex-boyfriend asks for a second chance.

[32][33] Pieterse's cookbook Sasha in Good Taste: Recipes for Bites, Feasts, Sips & Celebrations was published by Dey Street Books, an imprint of HarperCollins on October 8, 2019.

[44] At the start of season 25 of Dancing with the Stars, Pieterse revealed that she was diagnosed with polycystic ovary syndrome, which causes symptoms such as irregular periods and weight gain.