Before a crowd of some 35,000 in St Peter's square, the pontiff carried out the rite of canonization for 30 martyrs massacred in Brazil in the 17th century.
The two priests and 28 lay people were slaughtered by Dutch Calvinists and indigenous people in 1645, and in some cases had their hearts torn from their chests after being tortured and mutilated.
Catholicism's spread in southern Brazil started at the very end of the 1500s with Jesuit missionaries and priests from Portugal, but the arrival of Calvinists in the coming decades meant persecution for Catholics.
- 'Superpope' Francis T-shirts to help poor, needy
- Italian priest kidnapped in southern Nigeria: Vatican
- Pope Francis hits 40 million mark on Twitter
The new saints also included three teens slain in 16th-century Mexico due to their embrace of Catholicism. One of them, who had attempted to convert his father, was beaten to death by him.
The other two canonized were a priest from Spain who devoted his life to studying therapeutic plants in the 19th century, and an Italian priest who died in the 1700s after spending his life criss-crossing the southern end of his country.
Neither of those men are considered martyrs by the Catholic Church.
"The saints who were canonized today, and especially the many martyrs, point the way," Pope Francis said on Sunday. "They did not say a fleeting 'yes' to love, they said 'yes' with their lives and to the very end."
A tapestry on the facade of St Peter's Basilica shows Andrea de Soveral, Ambrogio Francesco Ferro, Matteo Moreira, and thirty martyrs murdered in Brazil in the 17th century. Photo: Tiziana Fabi/AFP.
Francis has frequently spoken out against the persecution of Christians, especially those targeted in the Middle East.
The Pope also announced he was calling a global assembly of bishops that would be devoted to the Amazon region, with an emphasis on indigenous people.
He said the aim was to find new ways to evangelize in that region, noting that indigenous people are "often forgotten" and face an uncertain future due to deforestation in the Amazon.