After completing his seminary studies, he desired to serve in the missions of the United States due to a shortage of priests there. In 1836, he traveled to New York, where he was ordained a priest. For several years, he ministered to scattered immigrant communities in rural areas, often traveling on foot or horseback.

In 1842, John joined the Congregation of the Most Holy Redeemer (Redemptorists), becoming the first member to profess vows in the United States. He served as a parish priest and later as the Redemptorist superior, known for his humility, hard work, and devotion to the poor and marginalized.

In 1852, he was appointed Bishop of Philadelphia. As bishop, St. John Neumann established the first system of Catholic parochial schools in the United States, significantly increasing access to education for immigrant children. He founded nearly 100 schools, built numerous churches, and introduced new religious orders to support his mission.

Despite his many responsibilities, St. John Neumann remained a humble and approachable pastor, deeply devoted to the Eucharist and the Blessed Virgin Mary. He died suddenly of a stroke on January 5, 1860, at the age of 48.

St. John Neumann was canonized by Pope Paul VI in 1977, becoming the first male American saint. His feast day is celebrated on January 5, and he is especially remembered as a patron of Catholic education and immigrants.