The first religious building on the site of the present church was a Roman monument, perhaps a temple of Attis, whose worship was probably the cause of the Christian persecution in Lyon from 177. In the 5th century, according to tradition, Eucherius of Lyon, 19th bishop of Lyon, built on the ruins of the building a basilica to contain the relics of the martyrs in Lyon, tortured in 177. The church received the name "Church of Holy Apostles". In the 6th century, the bishops were buried in the church, particularly Nicetius of Lyon, the 28th bishop. The body of the latter attracted a crowd and his presumed great miracles led the church to take his name. Saint Austregisilus was abbot here during the 7th century. In the early 8th century, the church has been ravaged by the Saracens and by Charles Martel. It was rebuilt in the 9th century, at the behest of the bishop Leidrade. Peter Waldo, in the 13th century, was a parishioner. His disciples, shocked by the wealth of the church, even set fire in 1253. From the 14th century to the late 16th century, the church was gradually rebuilt. In 1562, the notables gathered in the church, and in the 17th century, the aldermen were elected in the nave. It suffered the damage caused by several bands of Huguenot, which plundered the bishops of Lyon's tombs, then those of the French Revolution. After the French Revolution, the church served as flour warehouse. In the late 18th century, the project to transform the church into a gallery was abandoned after a petition signed by 100 notables. The sacristy was built in 1816, and the organ was installed in 1886. The church was in the 1970s the center of a popular neighborhood. Its presence was highlighted during its occupation by some prostitutes of the neighborhood in 1975 to express their anger towards police and social harassment. This church has often been perceived as a place of refuge and hospitality in the city. In the beginning in 1968, renovations undertaken by the management of the monument historique and the city of Lyon began, and they ended in 1998.
In the 17th century, theologian Bédien Morange was cantor and canon of Saint-Nizier. In the 19th century, the parish hosted famous spiritual people such as Frederic Ozanam, founder of the Saint-Vincent de Paul conferences, and Pauline-Marie Jaricot, foundress of the Propagation of the Faith. The church has been directed by priests and laity of the Emmanuel Community since 1996.
