Neumann was to be ordained in his home country in 1835. However, at the time, Bohemia was overstocked with priests and the bishop decided there would be no more ordinations. He contacted bishops all over Europe, but was continually turned away. Neumann, who had learned English by working in a factory with English-speaking workers, finally wrote the bishops in America. A bishop in New York agreed to ordain him in 1836.

Neumann was one of 36 priests for 200,000 Catholics in New York and his parish in western New York stretched from Lake Ontario to Pennsylvania. He spent most of his time traveling from village to village to visit the sick, to teach and to celebrate Mass.

He joined the Redemptorists, a congregation of priests and brothers dedicated to helping the poor and most abandoned in 1840. He served as a rector of parishes in Pittsburgh and Baltimore, and later became head of the Redemptorists in the United States.

In 1852, he was appointed Bishop of Philadelphia by Pope Pius IX. As bishop, he was the first to organize a diocesan Catholic school system, and he increased the number of Catholic schools in his diocese from two to 100.

The ability to learn languages that had brought him to America led him to learn Spanish, French, Italian, and Dutch so he could hear confessions in at least six languages.

Neumann died on January 5, 1860. He was declared a Saint of the Church in 1977 and his feast day is Jan. 5th.