Before the reign of Justinian II, Leontios' life is somewhat obscure. It is known that he was originally from Isauria. During the reign of Justinian II, Leontios was initially a patrikios, and strategos of the Anatolic Theme. Leontios led forces against the Umayyads, who were distracted by a war with the Zubayrids, at some point during the early reign of Justinian. The Umayyad caliph, Abd al-Malik ibn Marwan, sued for peace in 688, agreeing to increase the tribute payments from the Umayyad Caliphate to the Byzantine Empire, which had started under Emperor Constantine IV, to a weekly tribute of 1,000 pieces of gold, one horse, and one slave. Justinian invaded again around 692, because he felt the Umayyads were in a weak position. The Umayyads repulsed the Byzantine attackers and invaded North Africa and Anatolia. After the decisive defeat of the Byzantines by the Umayyads at the Battle of Sebastopolis, Justinian blamed Leontios, and had him imprisoned in 692.
Leontios was released in 695, in order to lead troops against the Umayyads, because Justinian feared losing the city of Carthage in the Exarchate of Africa. Leontios was made Strategos of Hellas upon his release. However, upon his release, Leontios launched a revolt, taking advantage of Justinian's upopularity. Justinian was vastly unpopular amongst the population, with the aristocracy opposed to his land policies, and the peasantry to his tax policies. Leontios led a march on the guards barracks, freeing those who were imprisoned by Justinian for opposing him. His force was joined by a host of Blues supporters, and then marched to the Hagia Sophia. He was met by Patriarch Kallinikos, who declared his support for Leontios' bid for the throne. Leontios then led his forces to the Great Palace of Constantinople, and captured Justinian and his ministers. They were brought to the Hippodrome, where Justinian's nose was cut off, a common practice in Byzantine culture, in order to remove threats to the throne. After Justinian's nose was cut off, Leontios exiled him to Cherson, and his ministers were dragged by their feet from wagons, and then burned alive.
In 698, the Umayyads, led by Caliph Abd al-Malik ibn Marwan, invaded the Exarchate of Africa, and seized Carthage. Leontios sent a fleet to retake the Exarchate, but the expedition failed. The forces initially were able to retake Carthage, however it was swiftly retaken by the Umayyads after the Byzantine fleet was decisively defeated just outside the harbor of the city. One of the commanders of this expedition, Apsimar, a Droungarios of German origins, started a revolt against Leontios, taking the regnal name Tiberios III, leading his men back to Constantinople, and allied himself with the Greens. His force seized Leontios, and cut off his nose and tongue, before sending him to live in the Monastery of Dalmatou, where he stayed under guard until 15 February 706, when Justinian II retook the throne with the assistance of the Bulgar king Tervel, and had both Leontios and Tiberios III dragged to the Hippodrome. There they were publicly humiliated, then taken away and beheaded.