The charter bus carrying about 40 people lost control around 10:30 a.m. on the snow- and ice-covered lanes of Interstate 84, according to the Oregon State Police.
The bus came to rest at the bottom of a snowy slope. More than a dozen rescue workers descended the hill and used ropes to help retrieve people from the wreckage in freezing weather. The bus driver was among the survivors, but had not yet spoken to police because of the severity of the injuries the driver had suffered.
Officials said the accident happened on the west end of the Blue Mountains at Cabbage Hill, and west of an area called "Deadman's Pass," where stretches of the highway tend to be icy in winter months.
The bus slid down the hill and landed upright, with little or no debris visible around the crash site.
St. Anthony Hospital in Pendleton treated 26 people from the accident, including some who were treated and then transported to other medical facilities, said hospital spokesman Larry Blanc.
In addition to the people who were transferred from St. Anthony to La Grand and Hermiston, Ore., and Walla Walla, Wash., Lt. Greg Hastings said. Others were taken directly to hospitals further away, including Boise, Idaho, and Portland, Ore.
I-84 is a major east-west highway through Oregon that follows the Columbia River Gorge.
Umatilla County Emergency Manager Jack Remillard said the bus was owned by Mi Joo travel in Vancouver, B.C., and state police said the bus was en route from Las Vegas to Vancouver.
A woman who answered the phone at a listing for the company confirmed with The Associated Press that it owned the bus and said it was on a tour of the Western U.S. She declined to give her name.
A bus safety website run by the U.S. Department of Transportation said Mi Joo Tour & Travel has six buses, none of which have been involved in any accidents in at least the past two years.
The bus crash was the second fatal crash in northeast Oregon on Sunday morning, due to icy conditions. A 69-year-old man died in a rollover accident at about 7:30 a.m. on I-84 near Stanfield.
A spokesman for the American Bus Association said buses carry more than 700 million passengers a year in the United States.
"The industry as a whole is a very safe industry," said Dan Ronan of the Washington, D.C.,-based group. "There are only a handful of accidents every year. Comparatively speaking, we're the safest form of surface transportation."