At least three Muslims were killed and 75 people seriously injured in violence that erupted between Buddhists and Muslims in southern Sri Lankan coastal towns.
US State Department spokeswoman Jan Psaki said Washington was concerned by inflammatory rhetoric that had incited the violence.
She said: "We urge the Sri Lankan government to fulfil its obligations to protect religious minorities, including protecting all citizens and places of worship, conducting a full investigation into the violence and bringing those responsible to justice.
"We also urge all sides to refrain from violence and exercise restraint."
Amnesty International said it was the worst outbreak of communal violence in Sri Lanka in years and there was a real risk of it spreading further. The human rights group said the Sri Lankan authorities should act immediately to end the anti-Muslim violence and to rein in groups targeting religious minorities.
The clashes erupted on Sunday in Aluthgama and Beruwela, two Muslim-majority towns on the Sinhalese-dominated southern coast, during a protest march led by the hardline Buddhist group Bodu Bala Sena, or "Buddhist power force".
Many independent analysts say well-coordinated violence against Muslims and Christians appears to have tacit state backing as those involved in previous attacks have yet to be punished. The government denies any collusion.