A patrician from Seleucia Sidera, Nikephoros was appointed finance minister (logothetēs tou genikou) by the Empress Irene. With the help of the patricians and eunuchs he contrived to dethrone and exile Irene, and to be chosen as Emperor in her stead on October 31, 802. He crowned his son Staurakios co-emperor in 803.
His rule was endangered by Bardanes Tourkos, one of his ablest generals, who revolted and received support from other commanders, notably the later emperors Leo V the Armenian and Michael II the Amorian in 803.
But Nikephoros gained over the latter two, and by inducing the rebel army to disperse achieved the submission of Bardanes, who was blinded and relegated to a monastery. A conspiracy headed by the patrician Arsaber had a similar issue.
Nikephoros embarked on a general reorganization of the Empire, creating new themes in the Balkans (where he initiated the re-Hellenization by resettling Greeks from Anatolia) and strengthening the frontiers. Needing large sums to increase his military forces, he set himself with great energy to increase the Empire's revenue. By his rigorous tax imposts he alienated the favour of his subjects, and especially of the clergy, whom he otherwise sought to control firmly. Although he appointed an iconodule, Nikephoros as patriarch, Emperor Nikephoros was portrayed as a villain by ecclesiastical historians like Theophanes the Confessor.
In 803 Nikephoros concluded a treaty, called the "Pax Nicephori", with Charlemagne, but refused to recognize the latter's imperial dignity. Relations deteriorated and led to a war over Venice in 806–810. In the process Nikephoros had quelled a Venetian rebellion in 807, but suffered extensive losses to the Franks. The conflict was resolved only after Nikephoros' death, and Venice, Istria, the Dalmatian coast and South Italy were assigned to the East, while Rome, Ravenna and the Pentapolis were included in the Western realm.
By withholding the tribute which Irene had agreed to pay to the caliph Hārūn al-Rashīd, Nikephoros committed himself to a war against the Arabs. Compelled by Bardanes' disloyalty to take the field himself, he sustained a severe defeat at the Battle of Krasos in Phrygia (805). In 806 a Muslim army of 135,000 men invaded the Empire. Unable to counter the Muslim numbers, Nikephoros agreed to make peace on condition of paying 50,000 nomismata immediately and a yearly tribute of 30,000 nomismata. With a succession struggle enveloping the caliphate on the death of Hārūn al-Rashīd in 809, Nikephoros was free to deal with Krum, Khan of Bulgaria, who was harassing his northern frontiers and had just conquered Serdica (Sofia).
In 811 Nikephoros invaded Bulgaria, defeated Krum twice, and sacked the Bulgarian capital Pliska; however, during Nikephoros' retreat, the Byzantine army was ambushed and destroyed in the mountain passes on July 26 by Krum. Nikephoros was killed in the battle, the second Eastern Emperor to suffer this fate since Valens in the Battle of Adrianople (August 9, 378). Krum is said to have made a drinking-cup of Nikephoros' skull.
By an unknown wife Nikephoros I had at least two children: