She began her career with small roles in short and independent films, and starred in the sitcom Tucker (2000–2001) and the soap opera Pasadena (2001).

[7] She was offered a full scholarship to attend New York University but declined, opting instead to directly pursue an acting career.

Two years later, she won the Desert Theater League's award for Most Outstanding Actress in a Musical for the title role in Annie.

She went on to perform locally as a child singer, which included alongside Frank Sinatra at a benefit event in Palm Springs.

[8] She moved to Los Angeles in 1997 to pursue an acting career,[9] beginning with minor roles in independent films and B movies.

[12] Released in 2002, White Oleander earned positive reviews, and Lohman's performance was met with widespread acclaim.

Matchstick Men earned Lohman's performance as an adolescent con-artist acclaim over her co-star Nicolas Cage,[16] while Big Fish saw her playing the younger version of Jessica Lange's character, for which USA Today wrote that "equally delightful is the Alison Lohman character's evolution into an older woman.

"[17] In 2005, Lohman appeared in Atom Egoyan's Where the Truth Lies which originally received an NC-17 rating for its graphic sexual content,[18] and emerged as a critical and commercial failure.

[26] Lohman starred in Sam Raimi's 2009 horror film Drag Me to Hell, taking the role after Elliot Page dropped out due to scheduling conflicts.