AmeriFlux scientists were early adopters of a network-enabled approach to ecosystem science that continues to transform the study of land-atmosphere interactions. In the 20 years since its formation, AmeriFlux has grown to include more than 260 flux tower sites in the Americas that support continuous observation of ecosystem carbon, water, and energy fluxes. Many of these sites are co-located within a similar climate regime, and more than 50 have data records that exceed 10 years in length. In this prospective assessment of AmeriFlux’s strengths in a new era of network-enabled ecosystem science, we discuss how the longevity and spatial distribution of AmeriFlux data make them exceptionally well suited for disentangling ecosystem response to slowly evolving changes in climate and land-cover, and to rare events like droughts and biological disturbances. More recently, flux towers have also been integrated into environmental observation networks that have broader scientific goals; in North America these include the National Ecological Observatory Network (NEON), Critical Zone Observatory network (CZO), and Long-Term Ecological Research network (LTER). AmeriFlux stands apart from these other networks in its reliance on voluntary participation of individual sites, which receive funding from diverse sources to pursue a wide, transdisciplinary array of research topics. This diffuse, grassroots approach fosters methodological and theoretical innovation, but also challenges network-level data synthesis and data sharing to the network. While AmeriFlux has had strong ties to other regional flux networks and FLUXNET, better integration with networks like NEON, CZO and LTER provides opportunities for new types of cooperation and synergies that could strengthen the scientific output of all these networks.