Controlling herbicide resistance (HR) and its associated environmental risks is impossible without integrating social and economic science with biophysical and technology aspects. Herbicide resistance is a dynamically complex and ill-structured problem involving coupled natural–human systems that defy management approaches based on simple scientific and technology applications. The existence of mobile herbicide resistance and/or herbicide tolerance traits add complexity because susceptibility to the herbicide is a resource open to all farmers, impacting the weed population. Weed scientists have extensively researched the biophysical aspects and grower perceptions of HR. They also recognize that the “tragedy of the commons” can appear when herbicide resistance is mobile across farms. However, the human structures and processes, especially private and public institutions that influence individual and group decisions about HR, have received little analysis. To start filling that gap, we discuss an integrative management approach to sustainable weed control that addresses the social complexity of farm heterogeneity. For example, the need for a private or public collective mechanism becomes apparent to address common-pool resource (CPR) aspects when one farmer's weed control actions influence their neighbors' situations. In such conditions, sole reliance on education, technical assistance, and other incentives aimed at changing individual grower behavior likely will fail to stem the advance of HR. Social science theories can be used to enrich the understanding of human interaction with the biophysical environment and identify key actors and social change processes influencing those interactions in the case of HR. The short-run economic advantages of herbicides such as glyphosate work against social change to address HR, including the development of collective actions when mobile HR conditions exist. We discuss seven design principles that can improve the efficacy and cost of such collective approaches and draw insights from CPR approaches outside of HR.