From the early beginning of his mission, the Prophet of Islam (pbuh) was ordered to introduce the God, who had come to his knowledge, to the pagans inhabited in Mecca and invite them to the monotheism and unitarianism. He knew that the racked intellectual and social structure of Mecca will create some difficulties in the way of his mission. In spite of the obstacle, which method was selected by the Prophet to confront pagans and how he could make a significant achievement? The findings of the present study which is on the descriptive-analysis method show that his policy for confronting pagans of Quraysh in Mecca and Medina was different. During the Meccan period, he tried to challenge the intellectual and theological system of the pagans and deny and reject polytheism through Islamic monotheism while in Medina he could challenge the political and religious identity of Meccan pagans after the revelation of verses of Jihad through the formation of new religio-political identity on the city-state of Medina and finally with the conquest of Mecca and the hegemony of monotheism discourse, he could prevail the unitarian thought in that city and made a brilliant achievement for himself.