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One Health initiatives have advanced zoonotic disease management by recognizing the interconnectedness of three sectors of governance (human, ecosystem, and animal) and by identifying options that can improve full‐system health. Although One Health has had many successes, its full realization may be inhibited by a lack of strategies to overcome simultaneous impediments in decision making and governance. Decision impediments that hinder management may include uncertainty, risk, resource limitations, and trade‐offs among objectives. Governance impediments arise from disparities in costs and benefits of disease management among sectors. Tools and strategies developed from decision science, collaboration, and negotiation theory can help articulate and overcome coinciding decision and governance impediments and enhance multisectoral One Health initiatives. In cases where collaboration and negotiation are insufficient to address disparities in cross‐sector costs and benefits, altering incentive structures might improve disease‐specific outcomes and improve the realization of One Health.