The Taliban claimed responsibility for the attack, which came as the insurgents intensify their nationwide spring attacks.
The guards were ambushed near Bagram base north of Kabul as they were driving home in a convoy late Monday, said district governor Abdul Shakoor Quddusi.
"They were all local residents serving as guards at Bagram," he said, adding that two other guards were wounded.
The Taliban claimed responsibility for the attack, which came as the insurgents intensify their nationwide spring offensive against Western and government targets.
Washington is soon expected to announce an increase in the US military deployment to bolster Afghan forces, who are struggling to contain the insurgency. American military commanders in Afghanistan have requested thousands of extra boots on the ground.
US troops in Afghanistan now number about 8,400, and there are another 5,000 from NATO allies, a far cry from the US presence of more than 100,000 six years ago. They mainly serve as trainers and advisers.
Bagram, around 50 kilometres (31 miles) north of Kabul, houses the largest contingent of US soldiers in the country.
The assault comes after seven American soldiers were wounded Saturday when an Afghan soldier opened fire at them inside a northern military base, the second "insider" attack in a week.
Analysts say such attacks are expected to increase this year as US troops engage with the Afghan military to double the size of its special forces, considered to be effective in the fight against insurgents.
The Afghan conflict is the longest in American history, with US-led forces at war since the Taliban regime was ousted in 2001.