D'Souza was appointed Bishop of Mangalore Diocese on 22 March 1965, and consecrated on 11 May 1965 by Abp James Robert Knox,
papal nuncio in India. He would retain the post until his death, thereby becoming the longest-serving bishop of the Mangalore Diocese. D'Souza was among the few participants in the final sessions of the
Second Vatican Council which took place from 1962 to 1965. He spearheaded the implementation of the renewal then proclaimed by the council, and became the first Indian bishop to implement the mind and spirit of the Universal Church as envisaged in the Documents of the Second Vatican Council. He was responsible for the introduction of vernacular services in the diocesan churches, where until then the masses were said in
Latin. The Bible and other liturgical texts were translated into Konkani during his tenure. He organised the welcoming arrangements for Pope
John Paul II during his historic visit to Mangalore on 6 February 1986. D'Souza's long tenure saw the establishment of several new parishes (mainly in the remote villages) and institutions such as family guidance centres. He founded a new mission outside the Mangalore Diocese at
Bidar in northern
Karnataka, where the number of Christians was small. He adopted the place as a missionary territory, and it later became a part of the
Roman Catholic Diocese of Gulbarga. D'Souza served as Chairman of the CBCI Commission of Vocations, in which capacity he founded the National Vocation Centre at
Poona. He also founded the Chair of Christianity at
Mangalore University in 1987. ==Death==