Serra, the first Hispanic American saint and the first saint to be canonized in the U.S., helped Spain colonize California in the late 1700s, converting tens of thousands of Native Americans to Catholicism in the process. Some Native American groups objected to the canonization of a priest who converted indigenous people to Christianity using force.
The pontiff addressed Serra's history in his homily.
"Junípero sought to defend the dignity of the native community, to protect it from those who had mistreated and abused it. Mistreatment and wrongs which today still trouble us, especially because of the hurt which they cause in the lives of many people."
After the mass, Francis met with Native Americans at the basilica to speak with them privately about the controversy.
More than 25,000 people attended the mass, including republican presidential candidate Jeb Bush and his wife, Columba. Another crowd gathered on the National Mall to watch the mass remotely.