Kristi Noem, the country's new secretary of homeland security, posted on X that she was "deploying every available US Coast Guard resource for search and rescue efforts in this horrific incident at DCA."
Police said fireboats had joined the operation on the river, where any work was complicated by the fact it was dark and close to freezing. Dozens of fire trucks headed toward the airport.
The FAA said a Bombardier regional jet operated by American Airlines subsidiary PSA Airlines "collided in midair" with a Sikorsky UH-60 helicopter as it approached for landing at Reagan at around 9:00 pm (0200 GMT). The plane had left from Wichita, Kansas.
US Senator Roger Marshall of Kansas said on X the collision was "nothing short of a nightmare."
American Airlines' CEO issued a video statement in which he expressed "deep sorrow."
Crowded airspace
Questions were expected to focus on how a passenger plane with modern collision-avoidance technology and nearby traffic controllers could collide with a military aircraft over the nation's capital.
The airspace around Washington is often crowded, with planes coming in low over the city to land at Reagan Airport and helicopters -- military, civilian and carrying senior politicians -- buzzing about both day and night.
The same airport was the scene of a deadly crash in January 1982 when Air Florida flight 90, a Boeing 737, took off but quickly plummeted, hitting the 14th Street bridge and crashing through the ice into the Potomac River. 78 people died.
Investigators concluded the pilot had failed to activate sufficient de-icing procedures.
The last major fatal US crash was in 2009, when Continental Flight 3407 from New Jersey to Buffalo, New York crashed and killed all 49 people aboard.