[5][6] Her paternal grandmother Colleen Rothenberg was a theatre actress who belonged to the Congregation Shomrei Torah synagogue in Santa Rosa, California.

[9] Rothe attended Cherry Creek High School[10] and then Boston University, graduating in 2009 with a bachelor's degree in Fine Arts,[9] and during that time she learned to play the violin, tap dance, and make pottery.

Rothe began acting under her birth name Jessica Rothenberg, and from 2010 to 2013, made minor appearances in shows such as The Onion News Network and played supporting roles in independent films such as The Hot Flashes and Jack, Jules, Esther and Me, among others.

[25][26] The show earned mixed reviews,[27] though critics praised the acting of Rothe and her co-star Scout Durwood.

"[28] In 2017, Rothe starred in the Christopher Landon horror film Happy Death Day—originally titled Half to Death—as Theresa "Tree" Gelbman.

[30][31] Happy Death Day was a significant box office success,[32][33][34] and was called a "starmaking" film for Rothe.

[43][44] In 2018, Rothe played Josie in the romance film Forever My Girl, which she accepted based on the themes of strength and female empowerment.

[46] The film was conceived by Landon before its predecessor was released,[47] and Rothe was initially hesitant feeling that a sequel could potentially retread the original.

[48][49] Kimber Myers of the Los Angeles Times called Rothe "one of the most magnetic new actresses on screen, equally capable of showing vulnerability and pain as well as a blithe, easy humor.

[57] Rothe said that "working with Gillian Flynn and the incredible cast in Chicago was a dream job, and I’m so excited for audiences to go through that emotional rollercoaster.

Though he gave the film a mixed review, Peter Sobczynski of RoberEbert.com said Rothe and co-star Melissa Leo "do strong work as those who represent the non-exploitative side of the rehabilitation world.