[1] While in Ghent he taught religious education at the diocesan secondary school in Eeklo from 1974 to 1980 and led courses in religion, philosophical anthropology and contemporary thought at Artevelde University of Applied Sciences (Sociale Hogeschool Gent) from 1977 to 1980.

[5][6] On 25 June 2010, De Kesel was appointed bishop of Bruges after the early resignation of Roger Vangheluwe[4] and installed there on 10 July 2010.

"[1][7] On 6 November 2015 Pope Francis named De Kesel to succeed André-Joseph Léonard as Archbishop of Mechelen-Brussels and Primate of Belgium.

He noted that the Bishop of Antwerp, Johan Bonny, had called for the recognition of same-sex relationships, while De Kesel by contrast said that universal respect, no matter one's sexual orientation, "is a value that the Gospel shares with modern culture.

He was disappointed the recent Synod on the Family had not resulted in allowing remarried Catholics to receive Communion, but thought the assembly demonstrated that the Church has a new mentality, adding: "For me, mercy is an important word, but somehow it still has something condescending about it.

"[3] De Kesel was elected president of the Belgian Episcopal Conference on 26 January 2016[11] and served until he retired as archbishop of Mechelen-Brussels in 2023.

[16] In 2022, together with other bishops of Flanders, he published a formula for the blessing of same-sex couples, underlining that it is not to be understood as recognizing a different form of marriage.

However its clearly at odds with the official Catholic stance that calls people with same-sex attraction to chastity, since it states that these unions "can also be a source of peace and shared happiness for those involved.”[17] Pope Francis accepted his resignation on 22 June 2023.