When he was about twenty-five, he married Khadija, a wealthy widow whose status elevated Muhammad's position in Meccan society. Muhammad and Khadija had four daughters and two sons, both of whom died in infancy. About fifteen or twenty years after his marriage, he began to have visions and hear mysterious voices. He sought solitude in a cave on Mount Hira on the outskirts of Mecca. One night during Ramadan, the traditional month of spiritual retreat, when Muhammad was about forty years old, an angel appeared to him in the form of a man and ordered him to;

Recite in the name of thy lord who created,
Created man from a clot;
Recite in the name of thy lord,
Who taught by the pen,
Taught man what he knew not.

Muhammad, fearing that he was being attacked by an evil spirit, fled down the mountain in terror. The voice called after him, "O Muhammad, you are the messenger of God, and I am the angel Gabriel." This revelation was soon followed by others about the one true God. Eventually, the angel told Muhammad to begin proclaiming God's message.

Muhammad slowly began to attract some followers, most of them young and of modest social standing, including his cousin Ali, the son of his uncle and protector Abu Talib. When Muhammad began to impugn the traditional polytheism of his native town, the rich and powerful merchants of Mecca realized that the religious revolution taking place under their noses might be disastrous for business, which was protected by the Meccan pantheon of gods and goddesses. The ruling elite ganged up against Muhammad and his followers, and began to persecute them. A few Meccans began to accept Muhammad's message, while other members of his clan came to support their kinsman out of family loyalty, even if they did not yet believe in his cause.

Muhammad's position in Mecca became hopeless when his wife Khadija and uncle Abu Talib died in quick succession. In 622 the local rulers of Mecca forced Muhammad and his small band of followers to leave the city. Muhammad accepted an invitation to settle in the oasis of Yathrib, located some eleven days (280 miles) north by camel, for the oasis had been nearly torn apart by wars between the clans, of which many were Jewish.

Muhammad's hegira from Mecca marks the beginning of a new polity. For the first time in Arabia members of a community were bound together not by the traditional ties of clan and tribe but by their shared belief in the one true God. Later believers, looking back on this event, recognized its seminal importance by designating it as the first year of their new era. In further recognition of this great event, the oasis of Yathrib came to be called Medina, "the city [of the Prophet]."

Muhammad, surrounded by his followers, lived in Medina for ten years, slowly winning over converts. Muhammad made repeated attempts to attract the Jews to his cause, for example, he directed that believers worship like the Jews in the direction of Jerusalem. Ultimately these attempts failed, and henceforth Muslims prayed in the direction of the Kaaba in Mecca. Muhammad's native town, which had long been a center of paganism, thereby became the center of the true religion, the focal point of the believers' daily prayer, and eventually the object of their annual pilgrimage.

Raiding and warfare were the primary economic activities of the new community in Medina, and the rich caravans organized by the Quraysh of Mecca were particularly attractive targets. In 628, Muhammad finally negotiated a truce with the Meccans and in the following year returned as a pilgrim to the city's holy sites. The murder of one of his followers provoked him to attack the city, which soon surrendered. Muhammad acted generously to the Meccans, demanding only that the pagan idols around the Kaaba be destroyed. Muhammad's prestige grew after the surrender of the Meccans. Embassies from all over Arabia came to Medina to submit to him. Muhammad's extraordinary life and career were cut short by his sudden death on June 8, 632, aged about sixty, less than a decade since he had set off from Mecca with his small band of followers.

Muslims to this day revere Muhammad as the embodiment of the perfect believer and take his actions and sayings as a model of ideal conduct. Unlike Jesus, who Christians believe was God's son, Muhammad was a mortal, albeit with extraordinary qualities. Today many Muslims believe that it is wrong to represent Muhammad, but this was not always the case. At various times and places pious Muslims represented Muhammad although they never worshipped these images.