She debuted as a fashion model in 1994, when she was only 11, using the stage name of Megumi Matsumoto (松本恵, Matsumoto Megumi).
Shortly after she appeared in various commercials and tv shows. In 1999 she announced her withdrawal from the entertainment business in order to continue her studies.
She came back in 2002 with the new stage name Rio Matsumoto, and one year later she played her first role in a movie, Cosmic Rescue: The moonlight generations. In 2005 she got her first important role, that of Tomie Kawakami in J-Horror Tomie: Beginning, directed by Ataru Oikawa, and based on the manga by Junji Ito.
In 2008 she worked with director Takashi Miike, in the sci-fi comedy God's Puzzle.
As a singer, she recorded her single Seraphita no Komoriuta in 2004
In 2007 Rio Matsumoto made her debut as a fashion stylist, creating wedding gowns. .