Headwater streams and wetlands are integral components of watersheds that are critical for biodiversity, fisheries, ecosystem functions, natural resource‐based economies, and human society and culture. These and other ecosystem services provided by intact and clean headwater streams and wetlands are critical for a sustainable future. Loss of legal protections for these vulnerable ecosystems would create a cascade of consequences, including reduced water quality, impaired ecosystem functioning, and loss of fish habitat for commercial and recreational fish species. Many fish species currently listed as threatened or endangered would face increased risks, and other taxa would become more vulnerable. In most regions of the USA, increased pollution and other impacts to headwaters would have negative economic consequences. Headwaters and the fishes they sustain have major cultural importance for many segments of U.S. society. Native peoples, in particular, have intimate relationships with fish and the streams that support them. Headwaters ecosystems and the natural, socio‐cultural, and economic services they provide are already severely threatened, and would face even more loss under the Waters of the United States (WOTUS) rule recently proposed by the Trump administration.