Manasses was indisputably of noble lineage, maybe even a son of the female line descended from Hugh Capet, King of France. He was a simple cleric before he succeeded Gervase de Bellême as archbishop. He was known to be enterprising and liberal and was reputed as "one of the columns of the church" by Lanfranc, Archbishop of Canterbury. Pope Gregory VII entrusted Manasses with several delicate missions, but the bishop's character was not held in esteem by his former colleagues, the lower clergy. Among them, he was reputed to be tyrannical, violent, corrupt, impatient, insolent, and disregarding of ecclesiastical regulations. His language gave cause to doubt his piety. According to Guibert of Nogent, "the archbishop of Reims would be a beautiful benefit [to the see], if he were not obligated to sing the masses!"
Eventually this reputation became public. In 1072, he began disputing with the monks of Saint-Remi over their rights of suffrage and tried to impose his own choice of abbot. Manasses responded to the abbey's resistance by excommunicating the monks and despoiling their goods. Gregory VII intervened to order Geoffrey, Bishop of Paris, to receive and absolve the monks fleeing into his territory. Papal legates were sent and, at a council held in Autun on 10 September, they condemned Manasses for simony and usurpation. He reacted by defending his conduct and trying to humiliate the legates. They in turn declared him a contumacious bishop.
Manasses appealed to the curia Romana and wrote letters to the pope demanding his privilege to convoke all the Gallican bishops and never to be summoned by legates. He made known his intention to be at Rome in Easter 1078. There he swore his innocence on the relics of St Peter. This was accepted, but returning to Reims, he acted even more haughtily and violently than before, punishing swiftly every opponent. At the suggestion of all the bishops of Gaul, the legates reopened the proceedings against him. He tried to bribe Hugh, Bishop of Die, with 300 pounds of gold, but this backfired and he was accused of bribery by Hugh at the Council of Lyon. Manasses refused to appear. He was deposed. The pope offered him a delay in his sentence if he would make reparations. He never did and was deposed by the Holy See on 27 December 1081.
Renaud de Bellay was elected to succeed Manasses, but the latter refused to relinquish the archiepiscopal palace. He was eventually chased from the city violently. Sources diverge as to where he fled: either the Holy Land, where he was captured by the Saracens, or Germany, where he accompanied the fellow excommunicate Henry IV, until he died.
Though Manasses was illiterate himself, an Apologia written by a cleric on his behalf and containing his ideas survives.