Moorhouse did her HSC year in 1978 at Vermont High School where her mother taught art, which is the same high school that Gillian Armstrong attended a few years earlier. She then enrolled in the Australian Film, Television and Radio School (AFTRS).

It was while studying at Australian Film, Television and Radio School (AFTRS) that Moorhouse completed her first short film entitled Pavane in 1983. Moorhouse then graduated from AFTRS in 1984 and started work as television script Editor. She created a twelve-part series called c/o The Bartons for the ABC in 1988—the series was based on one of her short films at AFTRS called The Siege of the Bartons' Bathroom. Some of the other television shows she worked on included The Flying Doctors, Out of the Blue, A Place to Call Home, and The Humpty Dumpty Man. Moorhouse made her feature film debut in 1991 with Proof. The idea for the film came from Moorhouse’s interest in blindness and photography. She initially intended on this being a short film but since she wasn’t able to secure the funding for a short she decided to make it into a feature film instead. It took Proof five years to go into production, but when it did it had a budget of 1.1 million dollars. The film ended up taking six weeks to shoot in Melbourne during the winter of 1990.

The success of Proof allowed Moorhouse to get bigger and better opportunities. She followed up that film with her first "Hollywood blockbuster" with How to Make an American Quilt (1995). The film had a talented cast which featured Anne Bancroft, Winona Ryder, Kate Nelligan, Dermot Mulroney, and Alfre Woodard. The film was met with mixed reviews.

Her next feature film was A Thousand Acres (1997). It was an adaptation of the Pulitzer Prize-winning novel by Jane Smiley. The film is about the relationship between a father and three daughters when tragedy is introduced into their lives. The film starred Jessica Lange, Michelle Pfeiffer, Jennifer Jason Leigh, and Jason Robards. This film, just like How to Make an American Quilt, was met with mixed reviews.

Moorhouse is married to Director P.J. Hogan. She was the Screenwriter for one of his films entitled Unconditional Love (2001). This was her second project with her husband as they both collaborated on Muriel's Wedding.

In 2012, Moorhouse directed her first play Sex with Strangers for the Sydney Theatre Company. In October 2014, she started filming The Dressmaker, with Kate Winslet and Judy Davis.

Moorhouse's most recent project is The Dressmaker (2015). The film stars Kate Winslet, Judy Davis, Liam Hemsworth, and Hugo Weaving. The film is based on the novel by Rosalie Ham and is about a dressmaker who returns to her home in Australia to take care of her ailing, mentally unstable mother.