In December 2019, U.S. President Donald Trump announced that his government would offer political recognition to Israeli settlements in the West Bank. The announcement reflected his latest effort to justify a series of domestic actions that his government took in Israel’s favor, including recognizing Jerusalem as Israel’s capital, abolishing certain programs, defunding programs in the Palestinian territories, relocating the U.S. embassy from Tel Aviv to Jerusalem, shutting down the U.S. consulate in Jerusalem and the PLO office in Washington, recognizing Israel’s annexation of Syria’s Golan Heights, and boycotting any and all activities at the UN Human Rights Council that were critical of Israel. The focus of this essay is to examine what backlash, if any, these American policies would produce in the Middle East. I argue that domestic and regional politics interact to produce regional responses to pro-Israel changes in American policy. The objectives of this article are accordingly to scrutinize the strategic implications of pro-Israel policies from the perspective of regional politics, explain how and why these policies may produce backlash, and anticipate several pessimistic views of Middle Eastern geopolitics that generally miss their complexities. We should begin by outlining, briefly, the trajectory of U.S. Middle East policy. Beginning with the presidencies of Woodrow Wilson and Harry S. Truman and culminating with those of Ronald Reagan and George W. Bush, most doctrinal and executive forms of American Middle Eastern policy were designed explicitly to maintain unequal relationships in America’s favor. Although cultures, civilizations, technology, and politics all change, modern statecraft has as its maximal aim the extension of continental hegemony and minimax regional hegemony. I would argue that the Middle East is now in such a state of conflict. While proximate issues may hold the headlines, permutations of quasi-regional conflicts will more likely determine the contours of mid-to-late 21st century regional politics.