Background: People with disabilities (PwD) have been facing multiple health, social, and economic disparities during the COVID-19 pandemic, stemming from structural disparities experienced for long time. This paper aims to present the PREparedness, RESponse and SySTemic transformation (PRE-RE-SyST): a model for a disability-inclusive pandemic responses and systematic disparities reduction. Methods: Scoping review with a thematic analysis was conducted on the literature published up to mid-September 2020, equating to the initial stages of the COVID-19 pandemic. Seven scientific databases and three preprint databases were searched to identify empirical or perspective papers addressing health and socio-economic disparities experienced by PwD as well as reporting actions to address them. Snowballing searches and experts’ consultation were also conducted. Two independent reviewers made eligibility decisions and performed data extractions on any action or recommended action to address disparities. A thematic analysis was then used for the model construction, informed by a systems-thinking approach (i.e., the Iceberg Model). Results: From 1027 unique references, 84 were included in the final analysis. The PRE-RE-SyST model articulates a four-level strategic action to: 1) Respond to prevent or reduce disability disparities during a pandemic crisis; 2) Prepare ahead for pandemic and other crises responses; 3) Design systems and policies for a structural disability-inclusiveness; and 4) Transform society’s cultural assumptions about disability. ‘Simple rules’ and literature-based examples on how these strategies can be deployed are provided. Conclusion: The PRE-RE-SyST model articulates main strategies, ‘simple rules’ and possible means whereby public health authorities, policy-makers, and other stakeholders can address disability disparities in pandemic crises, and beyond. Beyond immediate pandemic responses, disability-inclusiveness is needed to develop everyday equity-oriented policies and practices that can transform societies towards greater resiliency, as a whole, to pandemic and other health and social emergencies.