In 2002, Upham made her big-screen debut in the Chris Eyre-directed Skins, the first of many roles to draw on her American Indian heritage. That same year, she made her small-screen debut in another Eyre project, the TV movie Skinwalkers.
Two more TV movies and a film followed before Upham cut her long hair and gained weight to take on the role of a Mohawk Indian mother and widow who keeps her family afloat by smuggling illegal immigrants across the border in Frozen River (2008) -- a role for which she received an Independent Spirit Award nomination.
In this PBS American Mystery! feature, Navajo Tribal Officer Jim Chee (Adam Beach) and Lt. Joe Leaphorn (Wes Studi) are hot on the trail of a series of puzzling murders that immerse them in the spine-tingling, mystical world of Navajo witchcraft. Up against the clock, Chee and Leaphorn search desperately for the connection between the murders -- which occurred 120 miles apart. The film is adapted from Tony Hillerman's best-selling novel.