Riki Lindhome was born on March 5, 1979 in Coudersport, Pennsylvania, but grew up mostly in Portville, New York (near Buffalo). Her first break came when Tim Robbins cast her in his hit play Embedded, which was performed at the Public Theater in New York, Riverside Studios in London, and The Actor's Gang Theater in Los Angeles.

Shortly thereafter, Clint Eastwood cast her in her first film role, as Mardell Fitzgerald in Million Dollar Baby. She also wrote and directed the award-winning short film Life is Short. Since then she has acted in film, television, and commercials, and also performs as part of the Los Angeles comedy duo Garfunkel and Oates.