Kikuchi debuted in 1999, under her birth name, Yuriko Kikuchi, with the Kaneto Shindo–directed film Ikitai. Soon after, in 2001, she starred in the celebrated Kazuyoshi Komuri–directed film Sora no Ana, which was featured at several international film festivals, including the Rotterdam Film Festival. In 2004, she appeared in the much-commended Katsuhito Ishii–directed film Cha no Aji, which was selected for the Cannes Film Festival.
In 2006, she was cast by Japanese film producer Yoko Narahashi in the Alejandro González Iñárritu film Babel, where she played Chieko Wataya, a deaf-mute teenage girl, in a role for which she received international attention  and was nominated for numerous awards, including the Academy Award for Best Supporting Actress.
Kikuchi is Japan's only living female Academy Award nominee in an acting category. The only other nominee was Miyoshi Umeki, who won the Best Supporting Actress award in 1957 for Sayonara.