The incident was reported shortly after 5 a.m. near Main and E. 17th streets, just off the 10 Freeway, according to the Los Angeles Fire Department.
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According to the Los Angeles Police Department, the pursuit started when officers saw a gun being thrown out of a green minivan near Central Avenue and the 10 Freeway. That gun has since been recovered, authorities added.
Officers chased the vehicle for about two minutes before the collision.
The driver and the front passenger of the van were taken to the hospital with non-life threatening injuries. The two rear passengers, who appeared to not have been wearing seatbelts, both died.
"Our officers did begin first aid on them while they waited for paramedics to show up at scene," said Sgt. Hector Guzman. "Ultimately, one of those passengers inside the minivan was pronounced dead at scene. The other transported to a local hospital where he was pronounced dead at scene."
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Meanwhile, the bus driver and two other people aboard the bus, were treated at the scene but did not need to be taken to the hospital.
A statement from Metro's Rick Jager reads as follows, in part: "Early this morning, a vehicle being pursued by the LAPD crashed into a Metro Bus (Line 35) traveling southbound on Main Street as it was making a right hand turn onto 17th street. No serious injuries were reported on the bus."
Additional details about the crash were not released.