The killing of the cleric was the latest in a string of attacks on religious leaders allied to President Hamid Karzai's US-backed government.
Aljazeera's correspondent in Afghanistan said Salih Muhammad was killed after leaving his home in Sasain village, in Helmand province, and walking to his mosque on Wednesday.
A provincial government spokesman, Muhammad Wali, said the targeted man was the top cleric in the province and a member of the national Ulama Council.
Muhammad was also head of the Helmand province Shura Council, according to Aljazeera's correspondent.
His death comes a week after fighters shot dead a senior cleric and his wife in eastern Paktika province.
A few days earlier, another pro-government Muslim leader was killed in the southern city of Kandahar. In late May, one of the top national Muslim leaders, Abdul Fayaz, was also killed in the city.
US forces continue to engage
Meanwhile, the US military said on Wednesday that US and Afghan troops had killed 17 fighters in two days of clashes in southern Afghanistan.
The fighters were killed in clashes on Monday and Tuesday in the Taliban hotbed of Deh Chopan district in southern Zabul province, the military said in a statement.
"Seventeen enemy combatants were killed and six were captured as Afghan and US forces conducted operations south of Deh Chopan ... over the past two days," it said.
Another 23 people were being questioned regarding their involvement in the fighting, which was part of a sweep by US forces to deprive fighters of their hideouts in the rugged, mountainous area.
Spate of bloodshed
The clashes took place not far from Mian Nisheen district where the US military said 77 "militants" were killed in a three-day battle last month.
Some 140 Taliban fighters have been killed in the Zabul region since April, US military spokeswoman Lieutenant Cindy Moore said.
The latest fighting comes amid a spate of bloodshed that has left more than 700 people dead in three months and threatened to sabotage three years of progress towards peace in Afghanistan.
US and Afghan officials have warned that the violence is likely to worsen in the lead-up to legislative elections set for September.