He was born at Genazzano, the son of Agapito Colonna and Caterina Conti, between January 26 and February 20, 1369. He belonged to one of the oldest and most distinguished families of Rome. His brother Giordano became Prince of Salerno and Duke of Venosa, while his sister Paola was Lady of Piombino between 1441 and 1445.
Oddone studied law at the University of Pavia. He became apostolic protonotary under Pope Urban VI (1378–89), and was created Cardinal-Deacon of San Giorgio in Velabro by Pope Innocent VII in 1405.
In 1409 he took part in the Council of Pisa, and was one of the supporters of Antipope Alexander V. Later he confirmed his allegiance to Alexander's successor, John XXIII, by whom his family obtained several privileges, while Oddone obtained for himself the vicariate of Todi, Orvieto, Perugia and Umbria. He was excommunicated for this in 1411 by Pope Gregory XII. Oddone was with John XXIII's entourage at the Council of Constance and followed him in his escape at Schaffhausen on 21 March 1415. Later he returned to Constance and took part in the process leading to the deposition of John XXIII.