The accident happened at 11 a.m. during a range maintenance operation at the San Diego County coastal base.
The Marines were clearing the range of unexploded ordnance, and it was not a live firing range, a Marine official said. No further details were released.
The identities of the dead were withheld pending notification of relatives.
"We offer our heartfelt prayers and condolences to the families of the Marines lost today in this tragic accident," said Brig. Gen. John W. Bullard, commanding general of Marine Corps Installations West at Marine Corps Base Camp Pendleton. "Our first priority is to provide the families with the support they need during this difficult time."
The deaths come about eight months after a mortar explosion killed seven Marines during a live-fire training exercise in Nevada.
A military investigation determined human error was to blame for that accident. According to the probe's findings, a Marine operating a 60 mm mortar tube and ammunition did not follow correct procedures, resulting in the detonation of a high explosive round at the mortar position.
The investigation also determined that the mortar team involved in the accident had not conducted "appropriate preparatory training."