He was an Auxiliary Bishop of Dakota Territory under Bishop Martin Marty, the first Bishop of the Roman Catholic Diocese of Saint Cloud, Minnesota, Archbishop of Bucharest, Romania and Archbishop of Mocissus, Cappadocia. At the time of his death, he was allegedly being groomed to become the Papal Nuncio to Canada. He received his university education in Theology and Philosophy from Innsbruck.
Because of his talent for languages, he was offered the opportunity to accompany Bishop Greit to the First Vatican Council in Rome from November 1869 to Easter 1870.
He graduated with a doctor in Theology from Innsbruck in 1870 and was ordained the same year in Saint His talent in French, English and Italian as well as in his native language German brought him a post as professor in Rhetoric in Saint Georgen. After that he was first librarian and then canon at the diocese of Saint In 1879 he embarked upon his first travels to the United States, where he was invited by Archbishop Heiss of Milwaukee to teach dogmatics at the Metropolitan Seminary of Wisconsin.
Pope Leo XIII then appointed him in 1889 to be the first bishop of Saint Cloud in Minnesota. But because Zardetti did not take the many travels and changes of climate very well he soon expressed the wish to return to Europe.
The pope appointed him as archbishop of Bucharest in 1894, but the climate there agreed even less with him so that he resigned two years later.
He left numerous travel accounts and religious writings.
He was then appointed titular archbishop of Mocissus and took an apartment in Rome as a member of the curia.