State and local public health agencies are at the forefront of planning and responding to the health challenges of climate hazards but face substantial barriers to effective climate and health adaptation amidst concurrent environmental and public health crises. To ensure successful adaptation, it is necessary to understand and overcome these barriers. The U.S. Centers for Disease Control and Prevention Climate-Ready States and Cities Initiative (CRSCI) provides funding to state and local health departments to anticipate and respond to health impacts from climate change using the Building Resilience Against Climate Effects (BRACE) framework. This paper explores the barriers to and enablers of successful adaptation projects among BRACE West CRSCI grantees, including Arizona, California, Oregon, and the city and county of San Francisco. The barriers included competing demands such as the COVID-19 pandemic, dependence on partners with similar challenges, staff and leadership turnover, uncertain and complex impacts on at-risk populations, and inadequate resources. The enablers included effective partnerships, leadership support, dedicated and skilled internal staff, and policy windows enabling institutional change and reprioritization. These findings highlight effective strategies in the field that state and local health departments may use to anticipate potential barriers and establish their work in an environment conducive to successful adaptation.