The low-key tour, during which she has made no comment to reporters, has contrasted with the political tumult back home where her husband was set to score a big political win after days of acrimonious deadlock inside and outside the Senate over his Supreme Court pick.
The former model stepped off a plane at Cairo international airport wearing high-waisted white pants, a pleated white shirt and a black tie with a beige jacket hung over her shoulders.
She was welcomed by Egyptian First Lady Intissar Amer al-Sisi, an observant Muslim who wore an ankle-length blue dress and matching headscarf.
Security was tight with police deployed along the route and on rooftops as her convoy drove from the airport to the presidential palace.
The visit comes as security forces face a persistent jihadist insurgency in the Sinai Peninsula across the Suez Canal to the northeast.
The First Lady held a one-hour meeting with President Abdel Fattah al-Sisi and his wife at the palace, the longest of her tour, and was then driven to the US embassy before heading to the Pyramids of Giza.
During her whistlestop five-hour stay in Cairo, she was also scheduled to visit the new National Museum under construction next door to the Pyramids.
On the previous leg of her tour in Kenya, her choice of a white colonial-style pith helmet while on safari drew some criticism on Twitter, with one person comparing her look to that of a "colonial administrator".
Melania Trump, in Africa to promote her children's welfare programme, began her trip in Ghana, where she visited mothers and their newborns, and toured a former slave trading fort.
She then made a brief stop in Malawi where she toured a primary school.
On Thursday, her husband tweeted: "Our country's great First Lady, Melania, is doing really well in Africa. The people love her, and she loves them! It is a beautiful thing to see."