Otto began her acting career in 1986 at age 18 and appeared in a variety of independent and major studio films in Australia.

She rose to fame in the early 2000s for playing Éowyn in Peter Jackson's The Lord of the Rings film series, based on the classic fantasy novel of the same name by English author J. R. R. Tolkien.

[8] Otto's next role was in The Last Days of Chez Nous (1991), which portrayed the complex relationships between the members of an Australian family.

[8] In 1993, Otto co-starred with Noah Taylor in the sexually provocative comedy film The Nostradamus Kid, which was based on the memories of author Bob Ellis during the 1960s.

She played Dimity Hurley, a lonely young woman who competes with her older sister Vicki-Ann for the attention of a famous DJ from Brisbane.

[6] The film, directed by Samantha Lang, starred Otto as a teenager involved in a claustrophobic relationship with a lonely older woman.

Her involvement with Roxburgh made her a regular subject of Australian tabloid magazines and media at the time, a role to which she was unaccustomed.

[8] A small role in The Thin Red Line (1998) led to further film roles outside of Australia,[14] such as in Italy, where she co-starred as Ruth in the low-budget Italian film La volpe a tre zampe ("The Three-legged Fox"),[15] produced in 2001 and broadcast for the first time on Italian television in March 2009.

[24] Otto's performance earned her an Academy of Science Fiction, Fantasy & Horror Films nomination for Best Supporting Actress.

The film is a drama that portrays the story of Lindy Chamberlain, who was wrongfully convicted in 1982 of killing her baby daughter, Azaria, in one of the country's most publicized murder trials.

[26]Director Steven Spielberg, impressed by Otto's performance in The Lord of the Rings, called her to ask if she would play opposite Tom Cruise in the big-budget science fiction film War of the Worlds (2005).

In the series she plays Juliet Draper, a successful female executive who must rely on her friends to juggle the demands of a career and family in New York City.

[30] In 2013 Otto played the role of American poet Elizabeth Bishop opposite Glória Pires in Brazilian director Bruno Barreto’s Reaching for the Moon.

[31] Otto starred opposite Stephanie Sigman and Anthony LaPaglia in the horror prequel Annabelle: Creation, directed by David F.

[37] Otto made her theatrical debut in the 1986 production of The Bitter Tears of Petra Von Kant for the Sydney Theatre Company.

In 2002, she returned to the stage playing Nora Helmer in A Doll's House opposite her future husband Peter O'Brien.

[39] Her next stage role was in the psychological thriller Boy Gets Girl (2005), in which she played Theresa, a journalist for a New York magazine.