Mayor Ghulam Haider Hamidi, 65, was the third powerbroker from southern Afghanistan to be killed in just over two weeks.
Hamidi was killed as he left a city hall meeting. A suicide bomber detonated explosives hidden in his turban, killing the mayor.
The half-brother of President Hamid Karzai was also assassinated two weeks ago.
Five days later, Karzai's inner circle suffered another hit when gunmen killed Jan Mohammad Khan, an adviser to the president on tribal issues and a former governor of Uruzgan province, also in southern Afghanistan.
The Taliban have claimed responsibility for all three attacks.
The attacks come as the NATO troop draw down gets under way.
The Associated Press contributed to this story