"The bloodletting of Christians must end, and all who aid their killers must be punished," he said in a statement issued by his press office as he attends the G7 summit in Taormina, Italy.
"Terrorists are engaged in a war against civilisation, and it is up to all who value life to confront and defeat this evil."
Hours earlier, masked men in three pick-up trucks had attacked a bus carrying Coptic Christians on a visit to a monastery south of Cairo.
"This merciless slaughter of Christians in Egypt tears at our hearts and grieves our souls," said Trump, who met Egyptian President Abdel Fattah al-Sisi at a summit in Riyadh last week.
"Wherever innocent blood is spilled, a wound is inflicted upon humanity. But this attack also steels our resolve to bring nations together for the righteous purpose of crushing the evil organisations of terror, and exposing their depraved, twisted and thuggish ideology.
Christians have been targeted by Islamist militants across the Middle East in recent years, forcing thousands to flee a region which has been home to some of the oldest Christian communities in the world.
Trump said the United States "makes clear to its friends, allies and partners that the treasured and historic Christian Communities of the Middle East must be defended and protected.
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