The pontiff was welcomed by tens of thousands of people who lined the street to greet him.
He laid a bouquet of white flowers at the damaged Duomo cathedral of Carpi to honour the victims of the earthquakes.
Pope Francis hugs Carpi Bishop Francesco Cavina after celebrating a Mass in Piazza Martiri Square
The cathedral reopened last weekend after years of restoration.
"There are those who remain buried in the rubble of life," the Pope said in his homily before an estimated 20,000 gathered in the piazza outside the cathedral for an open-air Mass.
"There are those, like you, who with the help of God rise from the rubble to rebuild."
Another 50,000 people watched the Mass on large screens throughout the city of 70,000.
Following the homily, the Pope met with the families of those who lost loved ones in the disasters.
The 6.1 and 5.8 magnitude quakes killed 28 people in 2012.
Authorities have estimated the damage from the quakes at more than £11.5 billion.