NATO did not say whether it considered this an "insider" attack on foreign forces by Afghan allies.
In Washington, Pentagon press secretary George Little said 2,000 deaths is one of the "arbitrary milestones defined by others " that the U.S. administration does not mark.
"We honor all courageous Americans who have paid the ultimate sacrifice in Afghanistan to make the American people more secure," he said. "The fact of the matter is that America is safer because of all of those who have served in this war, including our fallen heroes."
In addition to the 2,000 Americans killed since the Afghan war began on Oct. 7, 2001, at least 1,190 more coalition troops from other countries have also died, according to iCasualties.org, an independent organization that tracks the deaths.
According to the Afghanistan index kept by Brookings, about 40 percent of the American deaths were caused by improvised explosive devices. The majority of those were after 2009, when President Barack Obama ordered a surge that sent in 33,000 additional troops to combat heightened Taliban activity. The surge brought the total number of American troops to 101,000, the peak for the entire war.
According to Brookings, hostile fire was the second most common cause of death, accounting for nearly 31 percent of Americans killed.
Tracking deaths of Afghan civilians is much more difficult. According to the U.N., 13,431 civilians were killed in the Afghan conflict between 2007, when the U.N. began keeping statistics, and the end of August. Going back to the U.S.-led invasion in 2001, most estimates put the number of Afghan civilian deaths in the war at more than 20,000.
In recent years, some of those casualties have generated a great deal of criticism from President Hamid Karzai and changed the way NATO forces carry out airstrikes. The overwhelming majority of civilian casualties are caused by insurgents - with the United Nations blaming them for more than 80 percent of the deaths and NATO putting that figure at more than 90 percent.
The number of American dead reflects an Associated Press count of those members of the armed services killed inside Afghanistan since the U.S.-led invasion began. Some other news organizations use a count that also includes those killed outside Afghanistan as part of Operation Enduring Freedom, the global anti-terror campaign led by then-President George W. Bush.
The 2001 invasion targeted al-Qaida and its Taliban allies shortly after the Sept. 11 attacks on the United States, which claimed nearly 3,000 lives.
Victory in Afghanistan seemed to come quickly. Kabul fell within weeks, and the hardline Taliban regime was toppled with few U.S. casualties.
But the Bush administration's shift toward war with Iraq left the Western powers without enough resources on the ground, so by 2006 the Taliban had regrouped into a serious military threat.
Obama deployed more troops to Afghanistan, and casualties increased sharply in the last several years. But the American public grew weary of having its military in a perpetual state of conflict, especially after the withdrawal of American troops from Iraq at the end of last year. That war, which began with a U.S.-led invasion in 2003 to oust Saddam Hussein, cost the lives of nearly 4,500 U.S. troops, more than twice as many as have died in Afghanistan so far.
Although Obama has pledged that most U.S. combat troops will leave by the end of 2014, American, NATO and allied troops are still dying in Afghanistan at a rate of one a day.
Even with 33,000 American troops back home, the U.S.-led coalition will still have 108,000 troops - including 68,000 from the U.S. - fighting in Afghanistan at the end of this year. Many of those will be training the Afghan National Security Forces that are to replace them.
"There is a challenge for the administration," O'Hanlon said, "to remind people in the face of such bad news why this campaign requires more perseverance."