Padovese made his simple vows in the Order of Friars Minor Capuchin on 4 October 1965 and his solemn vows on 4 October 1968. He was ordained a priest on 16 June 1973. He studied at the Pontifical University Antonianum and Pontifical Gregorian University. He has been a Professor of Patristics at the Pontifical University Antonianum, and for sixteen years he directed the Spirituality Institute at the same university. He also held chairs at the Pontifical Gregorian University and Pontifical Alphonsian Academy and had taught at various seminaries. He was appointed Apostolic Vicar of Anatolia on 11 October 2004 and consecrated a bishop on 7 November 2004. He had also been the president of Caritas Turkey.
Bishop Padovese was fatally stabbed in his summer residence in southern Turkey on June 3, 2010, and some reports claimed that he died en route to a hospital in the town of Iskenderun later that day. Witnesses claim that the perpetrator shouted the takbir (Allahu Akbar) during the assault, then severed his head. Catholic officials, including the Apostolic Nuncio to Turkey and papal spokesman Father Federico Lombardi, expressed "shock and sorrow" over the death of Padovese.
Bishop Padovese's driver (Murat Altun) for the last four and half years, who had been receiving treatment for psychological disorders, is suspected by Turkish police as the killer, and was detained by Turkish police on June 3. The suspect stated that he killed Padovese on a wahy (revelation), which identified him as Dajjal (the Antichrist) and recited the adhan loudly during his initial trial. Turkish police believe the murder was not politically motivated.
On January 22, 2013, Murat Altun was sentenced by an İskenderun court to 15 years imprisonment. Murat Altun's lawyer later stated that his client can be kept in prison for 10 years according to new Turkish law on criminal execution issues. He also drew attention to the point that his client is already in prison for 4 years, and said "The judicial holiday is ongoing in Turkey (2014 summer), when it finishes, my client will be transferred to a half-open prison , and he will continue his life in a half free manner" 
- Bishop Luigi Padovese Murdered, Capuchin website
- Bishop Luigi Padovese murdered, TRT website
- Piskopos cinayeti zanlısı tutuklandı
- Boris Kálnoky: Der erschütternde Tod des Bischofs Luigi Padovese, Die Welt, June 4, 2010
- "Fifteen-year sentence for killing of Bishop". Hürriyet Daily News. January 23, 2013. Retrieved January 28, 2013.