In his first major foreign policy address as president, Trump urged Muslim countries to ensure that "terrorists find no sanctuary on their soil" and announced an agreement with Gulf countries to fight financing for extremists.
He said that that the fight against terrorism "is not a battle between different faiths, different sects, or different civilizations".
"This is a battle between those who seek to obliterate human life and those who seek to protect it," he added.
"Terrorist don't worship God. They worship death."
The US is prepared to stand with those leaders in the fight against extremists but that those countries must take the lead, Trump said in his speech.
He urged them to drive extremists "out of your places of worship. Drive them out of your community. Drive them out of your holy land".
'Islam hates us'
Trump's speech has been touted as a major event - along the lines of a landmark address to the Islamic world by Obama in Cairo in 2009.
It will be especially sensitive given tensions sparked by the Trump administration's attempted travel ban targeting several Muslim-majority nations and his previous remarks on Islam.
In December 2015, Trump told a campaign rally he was calling for a "total shutdown" of Muslims entering the US "until our country's representatives can figure out what the hell is going on".
His words shocked many Americans, with Trump detractors noting that the US Constitution prohibits religious discrimination.
"I think Islam hates us. There is a tremendous hatred there. We have to get to the bottom of it," Trump said in a March 2016 interview with CNN.
Still, Trump has been welcomed warmly in Saudi Arabia, where he and First Lady Melania Trump were given an extravagant reception by King Salman and the rest of the Saudi royal family.
The trade deals announced on Saturday were said to be worth in excess of $380 billion and Trump proudly declared the first day of his visit "tremendous".
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