In 1342, he was raised to the position of cardinal. On the death of Clement VI, after the cardinals had each bound themselves to a particular line of policy should he be elected, Aubert was chosen (December 18, 1352); one of the first acts of his pontificate was to declare the pact to have been illegal and null.
His subsequent policy compares favourably with that of the other Avignon popes. He brought about many needed reforms in the administration of church affairs, and by his legate, Cardinal Albornoz, who was accompanied by Rienzi, he sought to restore order in Rome, where, in 1355, Charles IV was with his permission crowned, after previously having come under an oath that he would quit the city on the day of the ceremony.
It was largely through the exertions of Innocent that the Treaty of Brétigny (1360) between France and England was brought about. During his pontificate, John Palaeologus offered to submit the Greek church to the Roman See on condition of assistance being rendered against John Cantacuzenus. The resources at the disposal of the pope, however, were all required for exigencies nearer home, and the offer was declined.
Innocent was a liberal patron of letters, and, if the extreme severity of his measures against the Fraticelli are ignored, he retains a high reputation for justice and mercy. He died on September 12, 1362, and his successor was Urban V. Today his tomb can be found in the Carthusian monastery of Villeneuve-les-Avignon.