After quitting school, Moore went to work as a pin-up girl, modeled for European photographers, and worked at a collection agency. In the early 1980s, Moore posed for a series of photographs for Christopher Marrin featuring full frontal nudity. These photos went unnoticed until after she became a star, and were eventually published in a German magazine and later in North America. Moore's film debut was in the 1982 3-D science fiction/horror film, Parasite, which was a hit on the drive-in circuit, ultimately grossing $7 million. However, Moore was not widely known until she played the part of Jackie Templeton on the ABC soap opera, General Hospital, from 1982-1983. Appropriately, she also had an uncredited cameo at the end of the 1982 spoof Young Doctors in Love.

In the mid-1980s, she appeared in the youth-oriented films St. Elmo's Fire and About Last Night, and she was often listed as one of the Brat Pack, a name the media dubbed a certain group of top young actors at the time. After the commercial success of Ghost, Moore was given more prominent roles in A Few Good Men, Indecent Proposal, Disclosure and The Hunchback of Notre Dame for which she was the first actress to reach the $10 million salary mark. During the early 1990s, she was the highest paid actress in Hollywood. She never duplicated the success of Ghost and had a string of flops like The Scarlet Letter and The Juror. She then took more risks like shocking her fans with several breast enhanced topless scenes in Striptease, and shaving her head for G.I. Jane. They too failed at the box office and garnered mixed reviews. Meanwhile, Moore's Passion of Mind co-star Joss Ackland lambasted Moore by describing her as being "not very bright or talented". At the same time she produced and starred in a TV mini-series called If These Walls Could Talk, written by Nancy Savoca. A three-part series on abortion, Savoca directed two segments, including the one in which Moore played a single woman in the 1950s seeking a back-alley abortion. She was nominated for a Golden Globe for Best Actress for that role.

Demi Moore was a founding "celebrity investor" in the Planet Hollywood chain of international theme restaurants (modeled after the Hard Rock Cafe and launched in New York on October 22, 1991) along with Sylvester Stallone, Arnold Schwarzenegger and then-husband Bruce Willis. After a break from her acting career, Moore returned to the screen as a former member of Charlie's Angels gone bad in the 2003 film Charlie's Angels: Full Throttle. In 2006, she appeared in Bobby which featured an all-star cast including her husband Ashton Kutcher although they did not appear in any scenes together. On June 1, 2007, her most recent film, Mr. Brooks, was released. She appeared in Jon Bon Jovi's longform video "Destination Anywhere" as Janie. In 2006, Demi became the new face of the prestigious Cosmetic brand Helena Rubinstein.

• Happy Tears (2009) (post-production) .... Laura
• Bunraku (2009) (post-production) .... Alexandra
• The Joneses (2009/II) (post-production) .... Kate
  
• The Magic 7 (2008) (TV) (voice) .... U-Z-Onesa
• Mr. Brooks (2007) .... Det. Tracy Atwood
• Flawless (2007) .... Laura Quinn
• Bobby (2006) .... Virginia Fallon
• Half Light (2006) .... Rachel Carlson
  ... aka Half Light - Gefangen zwischen Licht und Schatten (Germany: DVD title)
• Charlie's Angels: Full Throttle (2003) .... Madison Lee
• "Will & Grace" .... Sissy Palmer-Ginsburg (1 episode, 2003)
       - Women and Children First (2003) TV episode .... Sissy Palmer-Ginsburg
• The Hunchback of Notre Dame II (2002) (V) (voice) .... Esmeralda
  ... aka The Hunchback of Notre Dame II: The Secret of the Bell (Australia)
• Passion of Mind (2000) .... Martha Marie/'Marty' Talridge
  
• Deconstructing Harry (1997) .... Helen/Harry's Character
• G.I. Jane (1997) .... Jordan O'Neill
• Destination Anywhere (1997) (V) .... Janie
• "Ellen" .... The Sample Lady (2 episodes, 1997)
  ... aka These Friends of Mine (USA: first season title)
       - The Puppy Episode: Part 1 (1997) TV episode (uncredited) .... The Sample Lady
       - The Puppy Episode: Part 2 (1997) TV episode (uncredited) .... The Sample Lady
• Beavis and Butt-Head Do America (1996) (voice) .... Dallas Grimes
• If These Walls Could Talk (1996) (TV) .... Claire Donnelly (segment "1952")
• Striptease (1996) .... Erin Grant
• The Hunchback of Notre Dame (1996) (voice) .... Esmeralda
• The Juror (1996) .... Annie Laird
• Now and Then (1995) .... Samantha Albertson