An estimated three million people had already gathered at Rizal Park two hours before the Mass began.
Twenty years ago, more than five million people attended a Mass celebrated here by Pope John Paul II.
The Vatican said Pope Francis would dedicate the service in part to the victims of Typhoon Haiyan, which devastated the country in 2013.
The Mass will be Pope Francis’ final full day in the Philippines, where there are 80 million Catholics, concluding his six-day tour of Asia.
Pope Francis arrived in a “popemobile” based on the design of the local minibuses, known as jeepneys.
Crowds sang and cheered as the pontiff stopped at various points to greet worshippers.
Some people had camped outside the park overnight to be the first ones admitted when the gates opened early on Sunday morning.
Before the final mass, Pope Francis held morning meetings with religious leaders and young people at the University of Santo Tomas which is the biggest Catholic university in Asia.
Pope Francis opened his meeting with over 20,000 students by remembering the 27-year-old woman who had died during his visit to Tacloban on January 17.
Earlier, police had reported that she had been killed when scaffolding collapsed after Saturday’s Mass.
The Pope then listened to several children speak about their experiences of growing up on the streets.
One of the children, 12-year-old Glyzelle Palomar, wept as she told her story and asked why God had allowed it to happen.
A visibly moved Pope Francis replied: “Only when we are able to cry are we able to come close to responding to your question.”
He added that the world needed to learn how to cry with those in need.
“Those on the margins cry. Those who have fallen by the wayside cry. Those who are discarded cry. But those who are living a life that is more or less without need, we don’t know how to cry,” he said.
Pope Francis, who comes from Argentina, was applauded when he told students that sometimes men were too macho, and that women had much to tell today’s society, seeing the world through different eyes, and asking different questions.
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