Obama's statement did not confirm the number killed or other details of the crash. Afghan President Hamid Karzai said that the crash killed 31 U.S. special operation troops and seven Afghan commandos.
A senior administration official said the helicopter that crashed in eastern Afghanistan was apparently shot down by insurgents in the deadliest single incident of the conflict for U.S. forces. The official spoke on condition of anonymity because the crash is still being investigated.
Obama, who learned of the incident at Camp David, issued a statement saying his thoughts and prayers go out to the families of those who perished.
"Their deaths are a reminder of the extraordinary sacrifices made by the men and women of our military and their families, including all who have served in Afghanistan," the president said. "We will draw inspiration from their lives, and continue the work of securing our country and standing up for the values that they embodied."
Obama said he also mourned the loss of seven Afghans "who died alongside our troops in pursuit of a more peaceful and hopeful future for their country."
Karzai sent his condolences to Obama, according to a statement issued by his office.
The Taliban claimed to have brought the helicopter down with a rocket attack, but similar claims in the past have proven to be exaggerated.
NATO officials in Afghanistan said they were trying to determine the details of what happened, but they acknowledged there was "enemy activity" in the area.
The toll Saturday surpassed the worst single-day loss of life for the U.S.-led coalition in Afghanistan since the war began in 2001 — the June 28, 2005 downing of a military helicopter in eastern Kunar province. In that incident, 16 Navy SEALs and Army special operations troops were killed when their craft was shot down while they were attempting to rescue four SEALs under attack by the Taliban.