The missile strike, the latest in a series targeting the man suspected of masterminding deadly attacks and beheadings in Iraq, killed four people, according to a doctor in the insurgent-controlled city.
Also Thursday, a U.S. Marine was killed in action in Anbar province, west of the capital, "while conducting security and stability operations," the military said in a statement. At least 850 Americans have died in Iraq.
In other violence, a homemade bomb exploded near the northern city of Mosul as a military convoy passed by, killing a coalition soldier and wounding two others, the military said. The soldiers' nationalities were not immediately revealed.
A roadside bomb detonated near a central Baghdad hospital, wounding a senior Iraqi Finance Ministry official and killing two of his guards, police and hospital officials said. Ehsan Karim, the head of the ministry's audit board, suffered slight injuries, said Col. Adnan Hussein, head of the Interior Ministry's information office.
Another roadside bomb exploded in the Amiriya district of the capital after a U.S. patrol passed through. Several Iraqi bystanders were killed and injured, Hussein said.
In other developments:
Al-Zarqawi, a Jordanian militant said to be connected to al Qaeda, is believed to be behind a series of coordinated attacks on police and security forces last week that killed 100 people. He is also believed to be behind the beheading of two hostages, American Nicholas Berg and South Korean Kim Sun-il.
Officials on Wednesday increased to $25 million the reward for information leading to his arrest, more than doubling the previous offering of $10 million. Osama bin Laden has a $50 million bounty on his head.
The U.S. attack on the safe house was launched after "multiple confirmations of Iraqi and multinational intelligence," said Brig. Gen. Mark Kimmitt, deputy operations director for the multinational force.
"This operation employed precision weapons to attack the safe house and underscores the resolve of multinational and Iraqi security forces to jointly destroy terrorist networks within Iraq," Kimmitt said.
Kimmitt did not mention casualties in his statement, but Dr. Loai Ali of the Fallujah General Hospital said four people were killed and 10 injured. There was no word on whether al-Zarqawi was in the house.
The raid came hours after rebels fired mortar rounds at a U.S. base on the outskirts of Baghdad's airport, wounding 11 soldiers and starting a fire that burned for more than an hour.
U.S. forces have mounted three previous airstrikes against suspected terrorist hideouts in recent days. On Friday, U.S. jets pounded a suspected al-Zarqawi hideout, killing up to 25 people, U.S. officials said.
Fallujah is believed to have become a stronghold of the al-Zarqawi's Tawhid and Jihad movement since Marines lifted their three-week siege in April and handed over security to a locally raised force commanded by officers from Saddam's army.
In other violence, clashes were reported overnight between militiamen loyal to radical Shiite cleric Muqtada al-Sadr and police in Amarah, southeast of Baghdad, but no casualties were reported, said Basim Bahloul, a senior police officer.
Meanwhile, police slapped a 9 p.m. to 6 a.m. curfew on the Shiite holy city of Najaf on Wednesday, a day after discovering about 150 pounds of explosives in a white BMW, police Brig. Ghalib al-Jazaari said.
One Libyan man who allegedly entered Iraq from neighboring Syria to fight U.S. forces was detained over the incident, al-Jazaari said.
The police chief also said militiamen loyal to al-Sadr kidnapped 25 policemen Tuesday in Najaf, 100 miles south of Baghdad, in response to the arrest of two of their colleagues but released 16 of them on Wednesday.
Ahmad al-Shibani, an al-Sadr spokesman, confirmed the kidnappings, but said all 25 had been freed. "We just wanted to teach them a lesson," he said.