The Safavid era constitutes one of the most significant periods in Iran's political history, marked by the official establishment of Twelver Shi'ism, which forged a new religious identity in opposition to the Sunni Ottoman world. Amidst this context, England, emerging as a nascent power in global trade and politics, sought to exploit the religious and political rivalry between the Safavids and the Ottomans to advance its own colonial interests. Adopting a historical-analytical approach, this study examines the foreign relations and policy of the Shi'a Safavid government with England within the framework of their confrontation with the Sunni Ottomans. The research data are analyzed based on historical sources, diplomatic correspondence, and reports by European travelers. The findings indicate that while Safavid foreign policy appeared to be shaped primarily by religious components and hostility toward the Sunni Ottomans, in practice, it was driven by considerations of power, economic interests, and the balance of power between East and West. Recognizing this religious schism, England leveraged its commercial and political ties with the Safavids to undermine the Ottoman position. In conclusion, the relationship between the Safavids and England serves as a prime example of the entanglement of politics, religion, and colonial interests during the 16^th and 17^th centuries.