The deaths occurred during "multiple, complex" bomb strikes that also killed one Afghan civilian, the U.S. military said in a statement, according to the Associated Press.
In October, a total of 55 American troops have been killed in Afghanistan thus far. The previous high was in August when 51 U.S. soldiers died amid a wave of Taliban insurgent attacks aimed at disrupting the first round of presidential elections.
The deadliest month of the war in Iraq for U.S. forces was November 2004, when 137 Americans were killed during the assault to clear insurgents from Fallujah.
"A loss like this is extremely difficult for the families as well as for those who served alongside these brave service members," Navy Capt. Jane Campbell, a military spokeswoman, told the AP. "Our thoughts and prayers are with the families and friends who mourn their loss."
Tuesday's deaths followed one of the worst days of the war for U.S. forces in Afghanistan. On Monday, a U.S. military helicopter crashed returning from a firefight with suspected Taliban drug traffickers in western Afghanistan, killing 10 Americans including three DEA agents. In a separate crash the same day, four more U.S. troops were killed when two helicopters collided over southern Afghanistan.
U.S. military officials insisted neither crash was the result of hostile fire, although the Taliban claimed they shot down a U.S. helicopter in the western province of Badghis. The U.S. did not say where in western Afghanistan its helicopter went down, and no other aircraft were reported missing.
Those casualties marked the Drug Enforcement Administration's first deaths since its Afghan operations started in 2005. Afghanistan is the world's largest producer of opium -- the raw ingredient in heroin -- and the illicit drug trade is a major source of funding for insurgent groups.
The increased death toll for U.S. forces comes as President Obama is considering a new strategy - possibly including tens of thousands of more troops -- for the Afghan war.
On the NewsHour, Senate Foreign Relations Committee Chairman John Kerry, who just returned from Afghanistan, said that if we "rush in with too many people too quickly, without having the support structure there that they need to make it sustainable, we're asking for the undermining of our own effort."
"You have got to show people like me and others that we have the civilian capacity to come in under underneath those troops, and the governance that's going to allow us to hold on, and the Afghan army members who will be in there with you, so it's not an American face; it's an Afghan movement," he said.
---- Compiled from wire reports and other media sources