Authorities say the bus was traveling eastbound on Interstate 10 near Tonopah when a man suddenly began to pummel the driver at 1:45 a.m. Passengers jumped up to intervene as the driver shouted, "Get this guy off me!"
"Other passengers came to the aid of the driver, and collectively, they were able to stop the bus," said Carrick Cook, a spokesperson for the Arizona Department of Public Safety, in a statement.
"He jumped on the bus driver and he said, 'I'm going to flip this bus,'" said Gregory Fort, a passenger on the bus.
The bus crossed the highway median, but it came to a stop before it entered oncoming traffic.
"I knew that once he hit that median, there was no way that we were going to come out of this, but he held it to the 'T,' even with the guy hitting him," said Fort.
When the bus came to a stop, the suspect and a female fled the scene into the desert. They returned about 30 minutes later and were arrested.
The male suspect was identified as 25-year-old Maquel Donyel Morris. Morris was reportedly hallucinating and wanted to get off the bus.
Morris is facing 48 counts of felony endangerment, 24 counts of assault and three counts of aggravated assault, Cook said. Bart Graves of the Arizona Department of Public Safety told the Associated Press that the suspect was taken to an area hospital for a drug-induced condition. It was unclear if the suspect's female companion would face any charges.
Of the 41 people on the bus, 26 were hospitalized with unknown injuries, according to Greyhound. Three passengers were airlifted, including one of the passengers who helped stop the attack on the bus driver.
Officials say the bus was en route to Dallas. Tonopah is about 50 miles west of Phoenix.
The Associated Press contributed to this report.