Safavid era (1501–1729) begins a new age in the history of Iran. With the beginning of the Safavid dynasty in Iran, Albuquerque, a Portuguese general, conquered Hormoz Island in southern Iran. ­Geographical ­discoveries, in general, and bypassing the Cape of Good Hope, in particular, in South Africa, changed traditional trade routes in Iran’s international trade. Under the new conditions that the Ottoman Empire held western areas of overland trade routes, Silk Road and Spice road failed in playing their former roles. On the other side, religious conflicts in the Safavid, Ottoman and Uzbek drew new plan of religious territories influencing road map. This paper tries to explain new map of Iran’s trade routes through ­studying Iran and economic and commercial requirements within 16th century.