Felix III was pope from March 13, 483 to 492. He was born into a Roman senatorial family and said to have been an ancestor of Saint Gregory the Great. Nothing certain is known of Felix until he succeeded St. Simplicius.

His first act was to repudiate the Henoticon, a deed of union, supposedly originating with patriarch Acacius of Constantinople and published by the emperor Zeno with the view of allaying the strife between the Monophysites and their opponents in the Orthodox Church. He also addressed a letter of remonstrance to Acacius. The latter proved refractory, and sentence of deposition was passed against Acacius.

In his first synod Felix excommunicated Peter the Fuller, a Monophysite who had assumed the See of Antioch against Papal wishes. In 484, Felix also excommunicated Peter Mongus, who had taken the See of Alexandria - an act which brought about a schism between East and West that was not healed until 519.