The United States has helped create and lead many international organizations (IOs). Yet in the last six years, the US announced its withdrawal from several IOs including the World Health Organization, UNESCO, and the Universal Postal Union. Do Americans care about US withdrawals from IOs? When do Americans support withdrawing from IOs and support candidates who propose this? We argue that Americans’ support for multilateralism tends to divide along party lines, and that IO withdrawal can activate those preferences. We also argue that framing an IO withdrawal as benefiting US national interests can make Americans more likely to favor IO exit. Data from four US survey experiments during the 2016–2020 Trump administration support these arguments. Democrats tend to oppose IO withdrawals while Republicans tend to support them. Further, results show that IO withdrawal (and how it is framed) affects candidate choice and policy support. This suggests that announcing IO withdrawal can be used to rally domestic electoral support. Still, the data also show that a large proportion of the US public values remaining in IOs, even when IOs are imperfect or challenging. In these cases, we note that sunk cost fallacies, status quo bias, and loss aversion may pose friction points for supporting withdrawal. Our findings have important implications for research on public opinion about international cooperation, backlash against IOs, and their life cycles.