The CH-53E Super Stallion is the largest helicopter in the US military. The names of the crewmembers will be withheld until 24 hours after their relatives are notified, the Miramar base said.
Marine officials have not identified the crew's squadron or the base from which it flew, according Capt. Morgan Frazer, spokeswoman for the 3rd Marine Aircraft Wing.
The 3rd Marine said the crash occurred during a routine training mission.
At approximately 2:35 p.m., a CH-53E Super Stallion from the 3rd Marine Aircraft Wing at MCAS Miramar crashed near El Centro, Calif., a city of about 44,000 people 10 miles from the U.S. -Mexico border.
It would be the deadliest crash for the Marines since a KC130T transport plane went down in July near the Mississippi Delta, killing all 16 aboard, according to an Associated Press report.
Nonetheless, the Super Stallion fleet was described as "inadequate" in November by Marine Lt. Gen. Steven Rudder, the service's deputy commandant for aviation. He said "our thoughts and prayers" are with the Marines.
Since late 2016, there have been two other major Marine CH-53 accidents.
The Super Stallion fleet is due to be upgraded to new CH-53K models known as King Stallions in the coming years.
He added, "We pray for their families" and the U.S. Marine Corps.
The cause of the crash is under investigation and no further information about what happened was immediately available on Wednesday morning.