Norman Duke Robert Guiscard of Apulia prepared to invade the Byzantine Empire in 1081 under the pretext of defending the succession of Constantine Doukas, who had been engaged to Robert's daughter Helena; at the same time, the Seljuks captured the town of Cyzicus.

Alexios was entrusted with a substantial army to defeat the Norman threat but conspired with his relative John Doukas to instead take the throne for himself. Alexios raised a rebellion against Nikephoros and was able to quickly surround Constantinople and put it to siege due to the lack of a defensive army. Nikeophoros was unable to secure the support of either the Seljuk Turks or Nikephoros Melissenos, his traditional rivals, and thus was forced to prepare to abdicate. Nikephoros decided that his only choice was to abdicate in favor of Melissenos, who was nearby in Damalis in Anatolia, and sent messengers to him across the Bosphorus; however, these messengers were intercepted by George Palaiologos, a general of Alexios, who persuaded them to support Alexios.

Alexios and his forces broke through the walls of Constantinople on 1 April 1081 and sacked the city; Patriarch Cosmas convinced Nikephoros to abdicate to Alexios rather than prolong the civil war. Nikephoros then fled to the Hagia Sophia and sought sanctuary inside of it. Michael, the logothete of Alexios, then escorted Nikephoros to the Monastery of Peribleptus, where he abdicated and became a monk. He died later that year.