The bus hit the center divider, and then clipped a Honda CRV that was not involved in the original accident.
The bus went off the right shoulder of the highway and down a 15-foot embankment before hitting a eucalyptus tree and coming to rest on a freeway off-ramp with its front end smashed and tree branches jutting into the vehicle.
Twisted pieces of metal, broken glass and torn clothing littered the ground around the wreckage.
The Trailblazer also landed at the bottom of the embankment, its roof caved in and doors crushed.
The bus was carrying 36 people. According to California Highway Patrol Officer Axel Reyes, the six people who died included four women and two men. Three of the women were in the overturned Trailblazer.
They have been identified as Stephenie Cordoba, 20, and Vanessa Gonzalez, 19, both of Fresno, and Sylvia Lopez Garay, 18, of nearby Dinuba.
The bus driver, identified as 57-year-old James Jewett of Sacramento, was among the dead at the crash scene. He died instantly of massive injuries, said Fresno County Coroner Dr. David Hadden.
"The front of the bus was destroyed and the front part of the bus was pushed into his driver's seat," Hadden said.
Two bus passengers were killed in the accident. They were identified as 60-year-old Epifania Solis of Madera and 79-year-old Tomas Ponce. Ponce and his wife, Sinforosa Ponce, 77, were heading to Merced to visit relatives. She was hospitalized with multiple injuries, the coroner said.
Nine people were taken to hospitals with moderate to critical injuries, according to officials.
The most seriously injured patients were taken to Community Regional Medical Center in Fresno, where attending surgeon John Bilello said one man remained in critical condition. The injuries included pelvic fractures and collapsed lungs.
Bus #30601 had left L.A. at 8 p.m. on Wednesday. Greyhound said it sent a relief bus to Fresno to pick up the uninjured passengers.
The cause of the accident has not yet been determined. A Greyhound spokesperson said they are cooperating with the California Highway Patrol in the investigation.
Hadden said his office planned toxicology reports on the drivers of the bus and SUV, with results expected in about a week. There were no obvious signs that anyone had been drinking, such as bottles in the vehicles, he said.
According to Greyhound, Jewett was hired in 1978 and had been a longtime driver.
Route 99 was closed for several hours following the deadly accident.
Greyhound has set up a hotline for friends and family at (800) 972-4583.
The Associated Press contributed to this report.