The three U.S. service members, two U.S. civilians, and the doctor were killed by an explosion while traveling to donate books to students in a school in the south, officials and the State Department said.
Secretary of State John Kerry said the Americans included a Department of Defense civilian and the Foreign Service officer.
"She tragically gave her young life working to give young Afghans the opportunity to have a better future," Kerry said. "We also honor the U.S. troops and Department of Defense civilian who lost their lives, and the Afghan civilians who were killed today as they worked to improve the nation they love."
Officials said the explosion occurred just as a coalition convoy passed a caravan of vehicles carrying the governor of Zabul province to the same event.
Another American civilian was killed in a separate insurgent attack in eastern Afghanistan, the U.S. military said.
It was the deadliest day for Americans since Aug. 16, when seven U.S. service members were killed in two attacks in Kandahar province, birthplace of the Taliban insurgency. Six were killed when their helicopter was shot down by insurgents, and one soldier died in a roadside explosion.
The latest attacks occurred just hours after U.S. Gen. Martin Dempsey, chairman of the Joint Chiefs of Staff, landed in Afghanistan for a visit aimed at assessing the level of training American troops can provide to Afghan security forces after international combat forces complete their withdrawal.
A U.S. official who spoke on condition of anonymity said several Americans and Afghans, possibly as many as nine, were wounded. The State Department said four of their staff were wounded, one critically.
Taliban spokesman Qari Yousef Ahmadi claimed responsibility for the attack in Zabul and said the bomber was seeking to target a coalition convoy or the governor.
"We were waiting for one of them," Ahmadi said in a telephone interview with the Associated Press. "It was our good luck that both appeared at the same time."
The deaths bring the number of foreign military troops killed this year to 30, including 22 Americans. A total of six foreign civilians have died in Afghanistan so far this year, according to an AP count.
Provincial Gov. Mohammad Ashraf Nasery, who survived the attack in Qalat, said the explosion occurred in front of a hospital and a coalition base housing a provincial reconstruction team. The team is composed of international civilian and military workers who train Afghan government officials and help with local development projects.
Nasery said the car bomb exploded as his convoy was passing the hospital. He said the doctor was killed, and two of his bodyguards and a student from the school were wounded.
"The governor's convoy was at the gate of the school at the same time the [coalition] convoy came out," the provincial police chief, Gen. Ghulam Sakhi Rooghlawanay, said. "The suicide bomber blew himself up between the two convoys."
Nasery said he thought his convoy was the intended target.