BAGHDAD—U.S. forces stepped deeper Friday into the Iraqi government’s fight to cripple Shiite militias, launching airstrikes in the southern city of Basra and firing a missile into the main Shiite stronghold in Baghdad.

The American support occurred as Iraqi troops struggled against strong resistance in Basra and retaliation elsewhere in Shiite areas—including more salvos of rockets or mortars into the U.S.-protected Green Zone in Baghdad.

It was the first time American jets have been called to attack militia positions since Iraqi ground forces launched an operation Tuesday to clear Basra of the armed groups that have effectively ruled the streets of the country’s second-largest city for nearly three years.

One militia barrage slammed into the headquarters of the Basra police command late Friday, triggering a huge fire and explosions when one of the rounds struck a gasoline tanker, police officials said.

Earlier Friday, U.S. jets struck a building housing militia fighters and blasted a mortar team that was firing on Iraqi forces, British military spokesman Maj. Tim Holloway said without further details.

Many of those groups are believed to receive weapons, money and training from nearby Iran, the world’s most populous Shiite nation.

The crackdown in Basra has provoked a violent reaction—especially from the Mahdi Army of anti-American Shiite cleric Muqtada al-Sadr. His followers accuse rival Shiite parties in the government of trying to crush their movement before provincial elections this fall.

Their anger has led to a sharp increase in attacks against American troops in Shiite areas following months of relative calm after al-Sadr declared a unilateral cease-fire last August.