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This case study comparatively analyzes public health and environmental cooperation processes and structures on the U.S.-Mexico border from emergence periods in the 1940s (health) and 1980s (environment), to a shared growth period in the 1990s, to the period of challenge that began with the new millennium and continued through the first Trump presidency. The study asks: How do actors adapt to threats and opportunities to advance transnational cooperation? How do transnational organizational fields cohere, given the centrifugal forces of states? I show how health and environmental professionals and activists used broader North American cooperation around issues like war and trade as opportunities to expand border health and border environment fields. I then document the rebordering that challenged these fields and draw attention to resilient identities and practices. I find that activists and professionals in the fields define themselves as transfronterizos, borderlanders with special transborder behaviors and worldviews that they argue are central for sustained advocacy for the border’s shared problems. I also explain how health and environment professionals and scientists create shared boundary objects that outlast political changes. These objects produce cognitive connections that help people understand the border as an interdependent region, with shared health and environmental problems, an empirical reality that persists despite state rebordering and conflict. Debordering involves actors creating and maintaining structural and cognitive connections that draw people and organizations together to address complex transborder problems. This historical comparative study brings attention to the people and practices that build resilient transborder connections, which can survive current threats to cooperation.