[5] She received her Bachelor of Fine Arts at the Carnegie Mellon School of Drama in Pittsburgh, where she said her professors advised her not to pursue acting.

[8][9] In 2017, Pedretti was cast in Mike Flanagan's Netflix supernatural horror drama series The Haunting of Hill House, in which she played Eleanor "Nell" Crain.

[12][13] Dakota Moss of MovieWeb wrote: "Pedretti's emotions to the role add a horrifying realism to the character, and viewers can feel all of Nell's pain and anguish to the very end.

[29][30][31] For season two, writers at Elle said Pedretti "delivered the perfect amount of spook and smolder to keep us on the edge of our seats for all ten episodes.

[33] In 2019, Pedretti played Leslie Van Houten in Quentin Tarantino's comedy-drama film Once Upon a Time in Hollywood,[34] which was a commercial success[35] and earned her nominations for several ensemble awards.

[41][42] Alan Sepinwall of The Hollywood Reporter wrote that "Her appealing vulnerability, and her talent for making the supernatural feel like something painfully real to Dani, do a lot of the heavy lifting this time around.

[43] Katerina Daley of Screen Rant said that her performance "has absolutely been a star-making one..."[44] Angelica Jade Bastién of Vulture magazine said Pedretti "has proven herself to be one of the most exciting young actors to watch".

[53][54] Also in 2021, she was announced to star in the film Lucky, based on the memoir of the same name,[55] in which she would be portraying writer Alice Sebold during her freshman year at Syracuse University.

[72][73] That same year, she made her Broadway debut in the Sam Gold directed adaptation of the Henrik Ibsen play, An Enemy of the People, at the Circle in the Square Theatre.

[74] Gold said of her casting that "She worked really hard in auditions and won the part for proving herself a really strong state actor who could take direction and take [it] all on her shoulders..."[3] Greg Evans of Deadline Hollywood believed Pedretti "is ready-made for her strong-willed, occasionally fretful, role".

[80] Pedretti has said her experience with The Haunting of Hill House made her comfortable with playing darker roles in the horror and thriller genres, and that she has "got a knack for" them.