Shortly before 6 p.m. Saturday, officials said the bus hit a truck that was parked on the shoulder of Interstate 90 in Cle Elum, Wash., a city about 80 miles east of Seattle.
That's when the bus careened onto its side.
Moments later, a car trying to avoid the accident crossed into the center median and crashed.
Officials said the bus was carrying soccer fans from a game in Seattle and was headed to Moses Lake.
It was not clear what caused the bus to crash into the truck.
A man and a woman on the bus were killed, and a man who was standing by the disabled truck was seriously injured and taken by helicopter to a Seattle hospital.
As many as 14 others in the three vehicles were believed to have minor injuries, but officials were not able to provide an exact count.
The Associated Press contributed to this report.