Lohman was born and raised in Palm Springs, California to Gary Lohman and Diane Dunham. She has one younger brother, Robert (born 1982). Her family had no industry connections, but at age nine, she played Gretyl in The Sound of Music at the Palm Desert's McCallum Theater. Two years later, she won the Desert Theater League's award for "Most Outstanding Actress in a Musical" for the title role in Annie. By the age of 17, Lohman had appeared in 12 different major productions and had been a backup singer for the likes of Frank Sinatra, Bob Hope and the Desert Symphony.

As a senior, she was an awardee of National Foundation of the Advancement of the Arts and was offered the chance to Tisch School of the Arts, but declined.

In 1997, Lohman moved to Los Angeles, California to pursue her acting career. For the next few years, her work consisted of science fiction B-movies (such as Kraa! The Sea Monster and Planet Patrol), television productions (Including the made-for-TV movie Sharing the Secret) and children’s films (such as Delivering Milo and The Million Dollar Kid). Also included was the dark urban drama White Boy.

She got her big break in the 2002 film White Oleander, an adaptation of Janet Fitch’s novel. She starred alongside Michelle Pfeiffer, Robin Wright-Penn and Renee Zellweger. Though the film was a box office failure (it opened to just $5.6 million in 1,510 theaters), Lohman's performance met with wide critical acclaim.

The following year, she appeared in Matchstick Men, directed by Ridley Scott. She starred with Nicholas Cage and Sam Rockwell, and though it was not a box office success, either, Lohman continued to gain praise. Later that year, she appeared in Tim Burton’s Big Fish, which continued her trend of appearing in films of high acclaim but little success.

She had no theatrical features in 2004, though she did voice the lead character in the re-dubbing of Nausicaa of the Valley of the Wind. In 2005 she appeared in Atom Egoyan’s Where the Truth Lies. The film originally received an NC-17 rating for its graphic sexual content, and, sure enough, it became box office poison soon afterwards. Her performance in particular was heavily criticized. Her next feature, The Big White, featured her alongside some very big stars (including Robin Williams, Holly Hunter and Tim Blake Nelson), but nevertheless went direct-to-video.