Health and human rights organizations have endorsed drug decriminalization to promote public health-oriented approaches to substance use. In the US, policymakers have begun to pursue this via prosecutorial discretion—or the decision by a prosecutor to decline criminal charges for drug possession in their jurisdiction. This study characterizes drivers of adoption, policy design and implementation processes, and barriers to impact and sustainability of this approach to inform evolving policy efforts promoting the health of people who use drugs (PWUD). We conducted n=22 key informant interviews with policymakers and national policy experts representing 13 jurisdictions implementing de facto drug policy reforms. Analyses were informed by the Exploration, Preparation, Implementation and Sustainment (EPIS) framework and analyzed using a hybrid inductive-deductive approach. Drivers of policy adoption included racial inequities, perceived failures of criminalization, and desires to prioritize violent crime given resource constraints. Three distinct policy typologies are described with varying conditions for eligibility, linkage to services, and policy transparency and dissemination. Public misinformation, police resistance and political opposition were seen as threats to sustainability. Given evidence that criminalization amplifies drug-related harms, many policymakers are adopting de facto drug policy reforms in the absence of formal legislation. This is the first study to systematically describe relevant implementation processes and emerging policy models. Findings have implications for designing rigorous evaluations on health outcomes and informing sustainable evidence-based policies to promote health and racial equity of PWUD in the US. •Arrest and incarceration of people who use drugs are linked to negative health outcomes.•Prosecutorial discretion can be used to enact de facto decriminalization of drug possession.•Little is known about how these nascent policies are developed and implemented in the U.S.•We describe shared and distinct features of emerging policies in 14 jurisdictions nationally.•Findings have implications for evaluating impacts on health and racial equity.