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 the Pope's final full day in the Philippines, where there are 80 million Catholics, concluding his six-day tour of Asia.
Philippine officials have estimated that as many as six million people may attend the Mass on Sunday afternoon, according to local media.
Some people camped outside the park overnight to be the first ones admitted when the gates opened early on Sunday morning.
"We are devotees of the Pope," Bernie Nacario told AFP news agency among the crowds in Manila.
"The Pope is an instrument of the Lord and if you are able to communicate with him, it is just like talking to God himself."