Johansson had her first significant screen breakthrough with her role as one of two orphaned teenaged sisters in Manny & Lo (1996), a coming-of-age drama directed by Lisa Krueger. Johansson, who shared the screen with Aleksa Palladino and Mary Kay Place, earned an Independent Spirit Award Best Actress nomination for her work in the film, and she soon found herself being tapped by Robert Redford to star as Kristin Scott Thomas' daughter in The Horse Whisperer (1998). Although the film met with a very mixed reception, Johansson was widely praised for her portrayal of a girl who loses her leg and her best friend in a horrific accident.

In 2000, the actress signed on to play one of the heroines (alongside Thora Birch) of Terry Zwigoff's screen adaptation of Ghost World, Daniel Clowes' celebrated comic about the adventures of two teen girls grappling with post-high school life. That same year, she starred in American Rhapsody, in which she portrayed a young girl who escapes communist Hungary in the 1950s and travels to the U.S.

Though she would take a brief detour into camp with the 2002 giant spider fiasco Eight Legged Freaks, the respect Johansson had gained in the film industry as a result of her previous dramatic roles found the young actress in high demand among indie directors while quickly catching the eye of the Hollywood elite. With Sofia Coppola's Lost in Translation, Johansson's touching performance as a young girl who strikes a tentative friendship with a washed up American actor (memorably portrayed by Bill Murray) while staying in Japan left no doubts regarding her dramatic skills in the eyes of many, and the rising starlet was soon cast in the lead of such subsequent films as The Girl with the Pearl Earring (2003) and The Perfect Score (2004).