[15] Daddario made her television debut at the age of 15, when she played victimized girl Laurie Lewis in the ABC daytime soap opera All My Children.

[16] She also had a recurring role as Neal Caffrey's love interest, Kate Moreau, in the USA Network procedural drama series White Collar.

[17] In 2012, Daddario starred in the music video for Imagine Dragons' song "Radioactive",[18] which surpassed 1 billion views on YouTube.

[21] She appeared in a four-episode arc as Lisa Tragnetti, a court reporter having an extramarital affair with one of the main characters; her nude scene with Woody Harrelson attracted much attention.

[22] The following year, she had a lead role as Blake Gaines in the disaster film San Andreas and made a cameo appearance in the pilot of the Fox comedy series The Last Man on Earth.

[23] [24] That same year, she made a guest appearance on American Horror Story: Hotel, portraying a fictionalized version of designer Natacha Rambova.

[25] In 2016, Daddario had a supporting role in the Nicholas Sparks romantic drama film The Choice, directed by Ross Katz.

[28] In 2018, Daddario appeared in the music video "Wait" by Maroon 5 and starred as Avery Martin in the romantic comedy When We First Met, opposite the film's co-writer Adam DeVine.

[29] Daddario made a cameo appearance as a scuba diver in Rampage, directed by San Andreas filmmaker Brad Peyton, but her scenes were cut from the final film.

[30] Daddario starred as Constance Blackwood in We Have Always Lived in the Castle, a film adaptation of Shirley Jackson's mystery thriller novel of the same name.

In 2019, Daddario starred in and produced two films, the romantic comedy Can You Keep a Secret?, based on the novel of the same name by Sophie Kinsella, and the horror thriller We Summon the Darkness, directed by Marc Meyers.