The brief visit, with Mattis later setting off to Israel, came after Sisi hit it off with Trump during a White House meeting earlier this month.
Sisi's visit marked a shift in relations after Trump's predecessor Barack Obama had given the Egyptian leader the cold shoulder for leading the military overthrow of Islamist president Mohamed Morsi in 2013.
Obama temporarily suspended military aid to Egypt following a bloody crackdown on Morsi's supporters.
Trump, however, has set aside criticism of Sisi's human rights record while pledging to maintain support for the key US ally which receives an annual $1.3 billion in military aid.
The meeting "addressed aspects of military and security cooperation between the two countries and ways to further enhance them," the president's office said in a statement.
Sisi told Mattis he wanted to "strengthen the ongoing military cooperation between the two countries," it said.
Mattis in turn "reiterated the US's commitment to reinvigorating these relations and broadening prospects for cooperation," it added.
After meeting Sisi, Mattis held talks with Defence Minister Sedki Sobhi at his headquarters, where he was received with a marching band playing the US national anthem.
"We've always had an open relationship," he told Sobhi.
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After the meeting, Mattis participated in a wreath laying ceremony at Cairo's Tomb of the Unknown Soldier.
He then prepared to fly on to Israel on the next leg of his tour, which started in Saudi Arabia.
In Egypt, the talks touched on the military's counterinsurgency in the Sinai Peninsula, where an Islamic State group affiliate has killed hundreds of soldiers and policemen.
Mattis "affirmed Egypt's pivotal role in the Middle East and commended its counter-terrorism efforts," the president's office said.
The insurgency in the Sinai took off after Morsi's ouster with the Islamic State group increasingly expanding its attacks to other parts of Egypt.
It claimed two church bombings in the cities of Alexandria and Tanta on April 9 that killed 45 people, months after a deadly Cairo church bombing.
On Thursday, the military announced it had killed a top IS cleric in Sinai air strikes, along with 18 other jihadists.
The Pentagon is also concerned with preventing jihadists from crossing Libya's porous border with Egypt and the reported presence of Russian troops in Egypt's western desert, which Cairo has denied.
After Israel, Mattis will return to the Gulf on Saturday for talks in Qatar.