As investigators probe the blast, Lieutenant General Stephen Townsend strongly defended U.S. behavior in the war and pushed back against accusations the United States had loosened safeguards meant to protect civilians as it ramps up the battle against Islamic State.
Still, he said increases in casualties were to be expected as the war against the insurgents entered its deadliest phase in the cramped, narrow streets of Mosul's Old City.
"It is the toughest and most brutal close-quarters combat that I have experienced in my 34 years of service," Townsend told Pentagon reporters, speaking from Iraq.
"What has not changed is our care, our caution ... our tolerance from civilian casualties - none of that has changed."
Watch: US Defense Secreatary responds to civilian killings in Mosul.
Rights group Amnesty International has said the high civilian toll in Mosul suggested U.S.-led coalition forces had failed to take adequate precautions to prevent civilian deaths.
Investigators combed through the rubble left by a March 17 explosion in al-Jadida district in west Mosul, where Iraqi forces backed by U.S.-led coalition air strikes are fighting to clear Islamic State militants from Iraq's second city.
One line of investigation is whether Islamic State rigged explosives that ultimately caused the blast that destroyed buildings. One estimate put the death toll at more than 200 people.
"My initial assessment is that we probably had a role in these casualties," Townsend told a Pentagon news briefing, speaking by teleconference.
"Now, here's what I don't know. What I don't know is were they (the civilians) gathered there by the enemy? We still have some assessments to do. ... I would say this, that it sure looks like they were."
The United States has about 5,200 troops in Iraq, the Pentagon says. Officials say two more companies of U.S. soldiers, just under 300 troops, are headed to Iraq on a temporary deployment.
