He was Bishop of Ostia e Velletri and Dean of the Sacred College of Cardinals from 1896 until his death.

In May of that year he was elected titular archbishop of Tamiathis and served as papal nuncio to Belgium from then until 1868, when he was moved to Portugal.

On 22 December 1873 Oreglia was created a cardinal by Pius IX and two years later he became Prefect of the Sacred Congregation of Indulgences and Relics.

As the only elector in the 1903 conclave with previous experience in electing a pope, and being the leader of the ultraconservative curial faction within the college who wanted a more intransigent pontiff than Leo, Oreglia is widely believed to have played a prominent role in the election of Giuseppe Sarto as Pius X.

Oreglia is also said to have vehemently protested against the announcement by Cardinal Jan Puzyna de Kosielsko regarding the civil veto of Emperor Franz Joseph of Austria against the name of Cardinal Mariano Rampolla, Leo's Secretary of State.