"I encourage you to sow seeds of love, confidently tread the path of dialogue, continue to show your goodness and kindness... and be builders of unity and peace," he told more than 80,000 devotees packed into the stadium in the Indonesian capital.
The 87-year-old pontiff earlier met Grand Imam Nasaruddin Umar at Jakarta's Istiqlal Mosque, where they signed a declaration warning against using religion to stoke conflict and appealed for action against climate change.
Francis's packed schedule on Thursday capped the first stop of a gruelling Asia-Pacific tour, the longest of his papacy, that will take him to Papua New Guinea on Friday and then to East Timor and Singapore.
He appeared to be in good spirits despite fears over his health as he addressed excited Catholics, who make up about three percent of the population of Indonesia, the world's most populous Muslim-majority country.
Anastasia Ida Ediati, a 59-year-old notary who went to the stadium with 200 other members of her parish, said she was filled with joy that she was lucky enough to be invited.
"We Catholics have such a charismatic and humble leader. His visit is especially meaningful for us, as many of us who are older may not have this opportunity again," she told AFP.
With President Joko Widodo in attendance, the pope entered Indonesia's national football stadium in a tactical vehicle built by an Indonesian state-run defence company.
- Conflict, climate -
The crowd had arrived on packed buses hours before, many of them wearing t-shirts showing the pope and taking group photos with the huge stadium in the background.
Pope Francis stood up to speak and start the mass despite humid conditions.
He had not travelled abroad since visiting Marseille in France in September last year and, as standard procedure, has been accompanied by his personal doctor and two nurses.
Unity between faiths has been the central theme of his trip and the declaration signed at the Istiqlal Mosque, Southeast Asia's largest, called for "religious harmony for the sake of humanity".
"The global phenomenon of dehumanisation is marked especially by widespread violence and conflict. It is particularly worrying that religion is often instrumentalised in this regard," it read.
"The role of religion should include promoting and safeguarding the dignity of every human life."
Francis underlined his message of unity in a speech before leaders of Indonesia's six recognised religions -- Islam, Protestantism, Catholicism, Buddhism, Hinduism and Confucianism.
"We are all brothers, all pilgrims, all on our way to God, beyond what differentiates us," he said.
The pope was welcomed to the mosque by a percussion band often used in Islamic ceremonies.
Once seated, he and Nasaruddin listened to a passage from the Koran recited by a young blind girl and a passage from the Bible.
- 'Save our environment' -
Francis also visited a "tunnel of friendship" that links the mosque to Jakarta's cathedral across the street, signing a section of the tunnel.
The declaration signed with Nasaruddin also pinpointed the environmental crisis as a threat to human civilisation and called for "decisive action" to counter global warming.
"The human exploitation of creation, our common home, has contributed to climate change," it read.
It said climate change had led "to various destructive consequences such as natural disasters, global warming and unpredictable weather patterns".
Francis has made several visits to Muslim-majority countries. He signed a document on human brotherhood with the Grand Imam of Al-Azhar, Sunni Islam's prestigious seat of learning, on a 2019 visit to the United Arab Emirates.
The trip to Indonesia is the third by a pope and the first since John Paul II in 1989.
Catholics number about eight million people in Indonesia, compared with the 87 percent, or 242 million, who are Muslim.
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