Nine Afghan troops and a policeman were also killed and several US soldiers were wounded in the fighting, which began on Tuesday.
American warplanes and helicopters pounded bands of fighters in clashes in Zabul and Kandahar, two restive provinces in the south of the country.
The Afghan troops died when fighters ambushed their patrol near Spin Ghar in Kandahar province on Wednesday evening, the worst-ever loss for the new US -trained army, the Defence Ministry said.
A US spokesman, Lieutenant Cindy Moore, said the troops were killed after climbing out of their trucks. Warplanes from the US-led coalition were called in to help them, and 20 fighters were killed in the ensuing battle, Moore said.
Over 18,000 US soldiers continue
to battle Taliban elements
"There was an estimated 20 killed in action," Moore said, adding that another six fighters were detained. Three Afghan troops and a US soldier embedded with the unit were injured, she said.
The US military also more than doubled the death toll from a clash the previous day in neighbouring Zabul province, saying that 44 fighters as well as an Afghan policeman had died in several hours of fighting in an area that has seen repeated large-scale fighting.
The rebels killed on Tuesday were a "mix of Taliban and anti-coalition militants" who appeared well-armed and disciplined, US spokesman Colonel James Yonts said. "They didn't flee. They stood and fought."
Ali Khail, spokesman for Zabul province's governor, said documents found on dead fighters showed two were Chechens and one was Pakistani, but US officials wouldn't release their nationalities, saying it might benefit their enemy.
The military had previously said 20 fighters died in the battle in Zabul's remote Dehchopan district, about 330km southwest of the capital, Kabul. The toll rose to 44 after troops found more bodies.
Yonts said four of the six Americans hurt in that battle were taken to a US military hospital in Germany. Five Afghan police were wounded.
Zabul and Kandahar lie along the Afghan border with Pakistan, in an area where Taliban-led fighters opposed to the government of US-backed President Hamid Karzai have revived their three-year-old insurgency after a winter lull.
Afghan Interior Minister Ali Ahmad Jalali said at a news conference Thursday that more than 100 rebels and at least 12 Afghan police had been killed in the past month - excluding most of the latest casualties.
"They didn't flee. They stood and fought"
Colonel James Yonts,
US army spokesman
Several civilians, as well as one US and one Romanian soldier, have also died.
The latest fighting coincided with the installation of a new commander of the 18,000-strong US-led coalition, who said Tuesday he would be "relentless" in battling the insurgency.
Leiutenant-General Karl Eikenberry said he would maintain the approach of bolstering Afghanistan's government while continuing the battle against fighters and their leaders -including Osama bin Laden and Taliban chief Mullah Omar.
The number killed on Tuesday was the highest since 2 August last year, when Afghan troops and US warplanes killed up to 70 suspected Taliban fighters in a daylong battle in the southeastern province of Khost.
Khost is across from Pakistan's Waziristan area, where rebels -including foreign fighters with al-Qaida links - are believed to have found refuge after the US invasion of Afghanistan in 2001.