The eldest daughter of actors Bruce Willis and Demi Moore, she made her acting debut opposite her mother in the coming-of-age drama Now and Then (1995).

She subsequently appeared in films such as Striptease (1996), Hostage (2005), The House Bunny (2008), Sorority Row (2009), and Once Upon a Time in Hollywood (2019).

She portrayed Joanne in the comedy film The House Bunny (2008) alongside Emma Stone, Colin Hanks and Anna Faris.

She had guest roles in television shows Miss Guided, Army Wives, CSI: NY, Medium, The Secret Life of the American Teenager, Hawaii Five-0 and Workaholics.

Willis portrayed Gia Mannetti in ten episodes of the teen drama television series 90210 (2009–2010).

In May 2013, The Hollywood Reporter announced that Willis will portray Zoe in the fourth season of Freeform's teen drama series Pretty Little Liars.

"[19] W magazine praised "her astonishing routines on the spring season of the show Dancing with the Stars, which she won with her partner Valentin Chmerkovskiy, that propelled Willis to new heights of fame.

"[19] In 2016, she had a voice role on the stop-motion sketch comedy series Robot Chicken, in the episode "Yogurt in a Bag."

On March 22, 2017, she had a recurring role in the third season of FOX's musical drama series Empire as Tory Ash.

On February 20, 2019, she was revealed to be "Lion" on the first season of Fox's reality singing competition series The Masked Singer.

"[25] Willis portrayed Joanna Pettet in the comedy drama film Once Upon a Time in Hollywood (2019) written and directed by Quentin Tarantino.

[40] On May 19, 2015, Willis and Chmerkovskiy were crowned the season's champions, winning over singer and actor Riker Lynch and army veteran Noah Galloway who took second and third place, respectively.