Boff entered the Franciscan Order in 1959 and was ordained a Roman Catholic priest in 1964. He spent the following years studying for a doctorate in theology and philosophy at the University of Munich, which he received in 1970. Boff's doctoral thesis studied in what measure the church can be a sign of the sacred and the divine in the secular world and in the process of liberation of the oppressed. He has since published his thesis as a book available in German, entitled Die Kirche als Sakrament im Horizont der Welterfahrung.

He became one of the best known (along with Gustavo Gutiérrez) of the early Liberation theologians. He was present in the first reflections that sought to articulate indignation against misery and marginalization with promissory discourse of the faith, leading to Liberation theology. He continues to be a controversial figure in the Catholic Church, primarily for his sharp criticism of the church's hierarchy, which he sees as "fundamentalist" ("A cardinal like J. Ratzinger, who publishes an official paper stating that the only true Church is the Catholic Church, and the others aren't even churches, that the only legitimate religion is Catholicism and the others don't even possess a faith, being just beliefs, perpetrates religious terrorism, besides being a grave theological error" ), but also for his past critical support of communist régimes.

He has always been an advocate of human rights causes, helping to formulate a new, Latin American perspective with "rights to life and the ways to maintain them with dignity". The work of liberation theologians helped lead to the creation of more than 1,000,000 "ecclesial base communities" ("Comunidades Eclesiais de Base" or CEBs) among poor Catholics in Brazil and in Latin America. The movement (and Boff) also criticised the role of the Roman Catholic Church in the social and economic order that oppressed the communities they worked in. Boff claimed to find much of the justification for his work in Chapter 1, No. 8 of Lumen Gentium ("Light of the Nations"), a document from Vatican II.

He is critical of secular power as well considering George W. Bush and Ariel Sharon's leadership to be similar to that of "fundamentalist terrorist state." He also criticizes despotic rulers in the Middle East: "Those [emirs and kings] are despotic, they do not even have a constitution. Though extremely rich, they maintain the people in poverty."

Boff said in an interview with the site "Comunità Italiana" (November 2001) about September 11 attacks on the United States of America: "For me, the terrorist attack of September 11 represents the shift towards a new humanitarian and world model. The targeted buildings sent a message: a new world civilization cannot be built with the kind of dominating economy (symbolized by the World Trade Center), with the kind of death machine set up (the Pentagon) and with the kind of arrogant politics and producer of many exclusions (...) For me the system and culture of capital began to collapse. They are too destructive." In the same interview he said that "One of the worst fundamentalisms is that of neoliberalism".

Authorities in the Roman Catholic Church did not appreciate his criticism of the church's leadership. They also felt his human rights advocacy had "politicized everything" and accused him of Marxism. In 1985, the Congregation for the Doctrine of the Faith, directed at that time by Cardinal Joseph Ratzinger (now Pope Benedict XVI), silenced him for a year for his book Church: Charism and Power. In the interview quoted above he accused Cardinal Ratzinger of "religious terrorism" (terrorismo religioso).

He was almost silenced again in 1992 by Rome, this time to prevent him from participating in the Eco-92 Earth Summit in Rio de Janeiro, which finally led him to leave the Franciscan religious order and the priestly ministry.

For most of his life Boff has worked as a professor in the academic fields of theology, ethics and philosophy throughout Brazil and also as lecturer in many universities abroad such as University of Heidelberg, Harvard University, University of Salamanca, University of Lisbon, University of Barcelona, University of Lund, University of Louvain, University of Paris, University of Oslo, University of Torino and others.

He has written more than 100 books, translated into the main languages of the world. In 2001 he was awarded the Right Livelihood Award in the Swedish Parliament.

He has received honorary doctorates, in politics from the University of Turin and in theology for the University of Lund. He has also been honored with various awards, within Brazil and the rest of the world, for his struggles on behalf of human rights for the weak, oppressed and marginalized.