The bus went through a chain-link fence off the side of Interstate 210 around 10 a.m. and ended up on its side down a dirt embankment between the freeway and railroad tracks in Irwindale.
Ambulances and helicopters converged on the freeway in eastern Los Angeles County and firefighters laid out red, yellow and green tarps to evaluate the injured.
Fifty-two people, mostly elderly, were hurt in the rollover with minor injuries, according to doctors and fire officials.
Eight needed immediate medical attention including five who were flown by helicopter to Los Angeles County-USC Medical Center. The patients, who suffered blunt force trauma, didn't speak English and needed translators. They were in guarded condition, said Dr. Leo Rodriguez.
TV news reports showed several people strapped to gurneys and being carried away.
The white bus, its front window knocked out, lay on its right side. Long skid marks led across three freeway lanes toward the bus. Weather was clear and dry.
Some of the passengers were able to get out on their own, while others needed to be rescued by firefighters, said Los Angeles County Fire Capt. Brian Jordan. Bystanders also aided in the rescue, Jordan said.
Huntington Memorial Hospital in nearby Pasadena treated three people including an 86-year-old man who had broken ribs. All were expected to survive, said hospital spokesman Kevin Andrus.
Fire officials said most of the passengers were senior citizens and many did not speak English.
The bus was from Da Zhen Travel Agency in the Los Angeles suburb of Monterey Park. It was heading to the San Manuel Indian Bingo and Casino in Highland, said Anna Zhang, an agency employee.
That large casino complex is about 40 miles east of the crash.
Da Zhen received a "satisfactory" rating during its last major review by federal inspectors, in 2010, according to U.S. Department of Transportation records.
Those records report that in the past two years, the company had no crashes among its nine buses. Two of its buses were cited for speeding in Arizona in February, while another was cited for "following too close" in May in Nevada.
Overall, the buses performed relatively well in mechanical inspections, failing just two of 30 over the past two years, according to the records. That 7 percent rate was significantly below the national average.
A schedule provided by the casino shows that Da Zhen runs 14 trips each day to San Manuel from various cities in Los Angeles County.
Interstate 210 is a commonly used foothill route to inland valleys and the desert east of Los Angeles. "Gamblers' specials" many catering to older people, frequently use it to bus tourists between the San Gabriel Valley and casinos in California and Las Vegas.
AP writers Robert Jablon, Alicia Chang and Greg Risling contributed to this report.