Los Angeles County Sheriff's Department officials said the 51-year-old bus driver, whose identity was not released, was rushed to a hospital, where he died of his injuries.
Metro officials said the Route 105 bus was heading east on Santa Monica Boulevard near La Cienega Boulevard shortly after 9 a.m. when a passenger opened fire on the driver, hitting him in the upper torso.
Authorities said the gunman, identified as a man in his 40s, was the only passenger on board. Witnesses reported seeing the man jumping out a rear window.
"When they arrived they discovered that the bus operator was suffering from a gunshot wound," Sheriff's Lt. Dave Dolson said. "They located the likely suspect that had surrendered himself to their custody."
A motive for the shooting was unknown.
A bomb squad was called in to investigate a suspicious-looking suitcase that had been left behind. No explosive device was found. However, two firearms, one apparently a shotgun and the other a handgun, were recovered from inside the bus.
Officials said the bus driver had worked for the Metropolitan Transportation Authority for five years.