Before the Mass, Pope Francis met former street children at the University of Santo Tomas
Tens of thousands of people lined the route of the Pope?s motorcade to catch a last glimpse of the pontiff on his way to Villamor Air Base.
A record six million people braved stormy weather to attend an outdoor Mass in the capital Manila on Sunday.
The Pope has spent a week in Asia, also visiting Sri Lanka, marking it as a growth region for the Catholic Church.
More than 80 million people are Catholic in the Philippines and the Pope was surrounded by adoring crowds everywhere he went.
On Monday, the streets were packed again as the leader of the Catholic Church made his way to the airport.
President Benigno Aquino led a departure ceremony on the tarmac as children sang and danced, chanting ?Pope Francis we love you?.
The Pope gave a final wave before boarding the Philippines Airlines plane.
On Sunday, the Pope?s Asia tour culminated with a world record for a papal gathering as he celebrated an outdoor Mass in Manila?s Rizal Park.
The previous record of five million people was during a Mass by John Paul II at the same venue in 1995.
During his visit, Pope Francis has spoken out repeatedly on the need to reduce poverty and inequality. He dedicated the final homily of his trip to children.
?We need to see each child as a gift to be welcomed, cherished and protected,? he said. ?And we need to care for our young people, not allowing them to be robbed of hope and condemned to a life on the streets.?
The BBC?s Rupert Wingfield-Hayes in Manila said as much as he could Pope Francis tried to identify with the poor in the Philippines; wearing a cheap plastic raincoat, riding in a pope-mobile modelled on the mass transport Filipino Jeepney and hugging street children.
He also pushed those in a position of power to help the poor and destitute.
The Pope also said the main reason he chose to visit the Philippines was to meet survivors of Typhoon Haiyan, which killed more than 7,000 people in November 2013.
On Saturday he visited Tacloban, the city in the central Philippines worst affected by the powerful storm.