The aircraft was taking off with three others on their last flight out of Guam after a four-month deployment, part of a continuous U.S. bomber presence in the western Pacific. After the crash, the other three bombers were being kept on Guam, said Maj. Eric Hilliard at Hickham Air Force Base in Hawaii.
At least one B-2 bomber had taken off safely from Andersen Air Force Base but was brought back when another aircraft plunged to the ground.
There were no injuries on the ground or damage to buildings, and no munitions were on board. Each B-2 bomber costs about $1.2 billion to build.
Thick, black smoke could be seen billowing from the wreckage at Andersen, said Jeanne Ward, a resident in the northern village of Yigo who was on the base visiting her husband.
Ward said she didn't witness the crash but noticed a rising plume of smoke behind the base's air control tower.
She said crowds began to gather as emergency vehicles arrived. "Everybody was on their cell phones, and the first thing everyone wanted to know was did the pilots make it out in time," she said.
The Air Force, without identifying the pilots, said one was medically evaluated and released, and the other was in stable condition at Guam Naval Hospital.
A board of officers will investigate what caused the bat-like aircraft to crash at 10:30 a.m., shortly after taking off from a runway. It was the first crash of a B-2 bomber, said Capt. Sheila Johnston, a spokeswoman for Air Combat Command at Langley Air Force Base in Virginia.
All 21 stealth bombers are based at Whiteman Air Force Base in Missouri, but the Air Force has been rotating several of them through Guam since 2004, along with B-1 and B-52 bombers.
The rotations are designed to boost the U.S. security presence in the Asia-Pacific region while other U.S. forces are diverted to fight in the Middle East.
The B-2 was first publicly displayed in 1988 and took its first flight a year later. The first bomber was delivered to Whiteman in 1993.
The bombers on Guam were scheduled to return to Missouri now that six B-52s from the 96th Bomb Wing at Barksdale Air Force Base, Louisiana, have arrived to replace them.
The distinctive B-2 is described as a "multi-role bomber" that blends stealth technology with a highly efficient aerodynamic design. It is able to deliver large payloads at great range and has been used in combat over Kosovo, Afghanistan and Iraq.
The accident occurred 11 days after a U.S. Navy plane crashed into the ocean about 20 miles northeast of Guam's Ritidian Point. Four aircrew members ejected from the EA-6B Prowler electronic warfare aircraft and were rescued by helicopter.
Guam is a U.S. territory 3,700 miles southwest of Hawaii.