The 12-hour battle began late Sunday in Shinkay district of Zabul province, a hotbed of resistance to the U.S.-backed Afghan government, the military said.
Spokesman Maj. Scott Nelson said about 40 militants attacked coalition soldiers on a search operation in Shinkay. The troops called for assistance from two Apache helicopters, which opened fire on the fighters.
"Skirmishes continued throughout the night, and the final battle damage assessment from the incident, from our soldiers on the ground, was 22," Nelson said.
Among the dead were three Arabs, the spokesman said. Another Arab was among three people arrested. No coalition forces were hurt, he said.
The U.S. forces seized a global positioning system, a video camera with tapes, four grenades and two assault rifles, he said.
Nelson declined to give the Arab fighters' nationalities, or say what was on the tapes.
Guerrillas loyal to the former ruling Taliban and their al Qaeda allies are active in southern and eastern Afghanistan, despite the presence of 18,000 coalition forces who have been hunting for terrorist suspects since late 2001.
In another clash Sunday, Nelson said Taliban gunmen ambushed a coalition patrol near the southern city of Kandahar. American soldiers returned fire without stopping.
"We engaged with them, but the number that were killed of the Taliban, I'm not sure," he said. No Americans were reported hurt.
Officials are forecasting a surge in violence in the run-up to Oct. 9 presidential elections, seen as crucial in Afghanistan's transition to democracy after a quarter-century of conflict. The Taliban have vowed to sabotage the polls.
Zabul, a rugged and remote region largely off-limits to foreign aid workers because of the security risk, has been the scene of much of the heaviest fighting in the past year, as the Taliban-led rebels have stepped up attacks.
In May and June, scores of insurgents were killed in fighting with U.S. and Afghan government forces, and since then there have been repeated smaller-scale clashes and rebel raids on Afghan government targets and security forces.
In a major move to reduce the power of the warlords who have ruled much of Afghanistan over the past 20 years, President Hamid Karzai this weekend ousted Herat governor Ismail Khan.
According to The New York Times, Khan's removal was officially described as a promotion to a ministerial position in the central government. But Khan declined the new post, and the change was widely seen as an effort to undermine Khan's power.
Khan has been a power broker in Afghanistan since the war against Soviet occupation. In March, Khan's troops clashed around Herat with forces loyal to another commander. Khan's son, Afghanistan's aviation minister, was assassinated.
Karzai had sent more than 1,000 members of the new, U.S.-trained national army and 300 German-trained national police to Herat province afterbetween troops loyal to Khan and those of rival warlords.
But they struggled to contain the unrest triggered by Saturday's announcement.
On Sunday, Khan supporters went on the rampage and clashed with Afghan and U.S. forces, looting and burning at least two U.N. compounds, other offices and vehicles. The unrest left three people dead and more than 50 injured.
Herat was calm on Monday morning, but aid workers were abandoning the city. The United Nations began flying some of its 51 foreign staff from the city to Kabul, spokesman Manoel de Almeida e Silva said.
About 50 other foreign relief workers were also heading for Kabul, said Nick Downie of the Afghanistan NGO Security Office, which advises aid groups on security.
The rioting in Afghanistan's wealthiest city was a blow to the war-torn country's faltering reconstruction and to Karzai's attempt to assert the authority of his central government in the runup the elections.
Khan, who also helped U.S. forces rout the Taliban three years ago, still has the loyalty of a sizable private army that he has been reluctant to disarm.
After a call from U.S. Ambassador Zalmay Khalilzad, Khan appeared on local television on Sunday evening to appeal for order in the city, an aide said.
"He called on the national army not to open fire on their countrymen and he asked the people of Herat to keep maintain peace and security, said the aide, Shah Mahmoud. "He said this city was built by labors of the people of Herat. Don't let it be damaged."
Most of the casualties in the violence at the weekend were civilians hit by bullets apparently fired by Afghan police and troops trying to keep order.
The U.S. military, which also had troops and helicopters in the area, said grenades were thrown by demonstrators but insisted it was not involved in any shooting.
Karzai condemned the rioters, who also burned the office of a Danish aid group and wrecked the local branch of the Afghan human rights commission. He said they were damaging Afghanistan's fragile peace process.
"That's not what this country wants, and that's not what the people of Herat want," Karzai said Sunday. "We will deal with that strongly."