Cassel, who started for the Kansas City Chiefs last season, takes over from an injured Christian Ponder. Ponder suffered a rib injury early in last week's game against Cleveland but was able to finish the contest.
However, Vikings Coach Leslie Frazier said the threat of additional injury to Ponder's fractured rib was behind the quarterback switch. Ponder's practice time was limited this week and Cassel ran most of the plays with the first-team offense.
"I feel like I'm ready to go, I've had a good week of practice," Cassel said. "Now it's about going out there and executing on Sunday."
Cassel, who started his career with four seasons with the New England Patriots, was signed by Minnesota last spring after four seasons in Kansas City. He was released by the Chiefs after they traded with San Francisco for quarterback Alex Smith.
Ponder has completed 59 percent of his passes for 691 yards. He has two touchdown passes and five interceptions as the Vikings are off to an 0-3 start.
Pittsburgh is also 0-3 going into Sunday's game in London, one of two the NFL will have in England this year. San Francisco plays Jacksonville Oct. 27 in the other.