According to the California Highway Patrol, the crash was reported shortly after 11 a.m. on SR-60 westbound, west of Jack Rabbit Trail.
Investigators say a silver BMW 328i, driven by a 54-year-old man from Riverside, was heading eastbound when its left rear tire came off and became airborne.
The tire flew over the center divider wall into the westbound lanes, where a 68-year-old man from Los Angeles, who was driving in a white Toyota Sienna, struck the tire.
The tire slammed into the windshield and roof of the man's Toyota before he lost control of the vehicle and crashed into the center divider wall. The Toyota then continued and crashed into a dirt embankment, CHP said.
The 68-year-old man behind the wheel was pronounced dead at the scene, according to CHP. A female passenger was transported to a local hospital with minor injuries.
CHP said the driver of the BMW that lost the tire was not injured.
The crash is still under investigation, and anyone with information is encouraged to contact the investigating officer, Officer J. Esparza, or Public Information Officer R. Palomera at the California Highway Patrol San Gorgonio Pass Area office -- 195 Highland Springs Avenue, Beaumont, California 92223 (951) 846-5300.