The coalition said Tuesday it launched the strike in support of the Kurdish-led Syrian Democratic Forces, who are fighting to drive the extremists from their last tiny stronghold near the border with Iraq.
It said the strike occurred Monday as Islamic State was using the mosque to direct attacks and employ suicide car bombs against the SDF.
The coalition's deputy commander, Maj. Gen. Christopher Ghika, was quoted in the statement as saying "this mosque lost its protected status when Islamic State deliberately chose to use it as a command and control center."
The SDF on Saturday launched its final push to clear the area after months of fighting.
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SDF spokesman Mustafa Bali tweeted that the offensive began Saturday after more than 20,000 civilians were evacuated from the Islamic State-held area in the eastern province of Deir el-Zour.
Syrian opposition activists reported that Islamic State militants have attacked U.S.-backed fighters near an oil field in the country's east, triggering airstrikes by the U.S.-led coalition.
The Syrian Democratic Forces launched its offensive to end the Islamic State presence in Syria in September, a battle that left hundreds of fighters dead on both sides. The Syrian Democratic Forces has driven Islamic State from large swaths of territory it once controlled in northern and eastern Syria, confining the extremists to a small pocket of land near the border with Iraq.