The KC-130, an aircraft that the Marines can use to refuel planes in the air as well as carry cargo, crashed in Leflore County at about 4 p.m. CT, the service said.
Federal Aviation Administration officials contacted the Marines when the aircraft disappeared from air traffic control radar over Mississippi, officials said.
The flight originated from Marine Corps Air Station Cherry Point in eastern North Carolina, the Marines said. The service hasn’t commented on the crew’s mission, the itinerary or the destination.
The service members’ names weren’t immediately released.
“While the details of the incident are being investigated, our focus remains on providing the necessary resources and support to the family and friends of these service members as they go through this extremely difficult time,” the Marines said in a news release.
Flames and dark smoke rose from part of the wreckage in a field off the highway, video from WDBD showed.
President Donald Trump called the crash “heartbreaking” on Twitter.
“Melania and I send our deepest condolences to all!” the President tweeted.
Interior Secretary Ryan Zinke, who had long service as a Navy SEAL, was among officials posting condolences on social media. “Please join me in praying for or sending good thoughts to the families and unit of the Marines we lost tonight in the C 130 crash,” Zinke wrote on Twitter.
U.S. Sen. Thad Cochran, R-Mississippi, posted on Twitter: “Deeply saddened by the loss of life in today’s @USMC KC-130 crash in the Mississippi Delta. Our thoughts & prayers are w/everyone involved.”
Often used for airborne refueling, the KC-130 also can be used to deliver cargo, troops and equipment by landing or parachuting them in, and for evacuating fighting forces from a battle area.
The latest version of the KC-130, the KC-130J, can weigh as much as 164,000 pounds on takeoff, and has a maximum range of more than 4,200 nautical miles with external tanks, its maker, Lockheed Martin Corp., says.
The first KC-130s appeared in 1962. Its normal range of 1,150 miles as a tanker and 3,300 miles on cargo missions gives it access to the entire war arena.
2015 crash blamed on misplaced goggles case
A US Air Force investigation blamed the crash of the C-130J on the misuse of a night-vision goggles case that the pilot had placed in front of the cockpit yoke while the plane was on the ground.
The pilot put the case there to prop up part of the plane’s tail to help the loading team deal with some tall cargo, but the case was never removed, and when the plane’s nose pitched up too far, the case blocked the yoke when the pilot tried to move it forward, the investigation report said.
Correction: An earlier version of this story incorrectly reported the FBI is at the scene of the crash. The FBI told CNN on Tuesday that it is not at the scene.
CNN’s Barbara Starr, Dave Alsup, Thom Patterson and Amanda Jackson contributed to this report.