Misty Anne Upham, born in Kallispell, Montana, grew up in south Seattle, the fourth of five children. She began her career at the age of thirteen when she joined a community theater group, Red Eagle Soaring. What began as a summer workshop soon turned into a full-time job. By the age of fourteen she was writing and directing short skits and performing on tours throughout the northwest. In the next four years she would be accepted to several Seattle theater companies, all while attending high school. Her first break came in 2001 when she landed the role of Mrs. Blue Cloud in Chris Eyre's sophmore project Skins (2002), where she portrayed a victim of domestic abuse on the Pine Ridge reservation. She also had a large role in the family drama August: Osage County (2013), playing Johnna Monevata, a live-in housekeeper.
Misty died in 2014, in Auburn, Washington, of blunt-force trauma.