Abstract This paper highlights Muhammadiyah’s religious and social engagement and praxis in dealing with the pandemic in Indonesia. As Indonesia’s largest modernist Islamic organisation with approximately 30 million members, Muhammadiyah has been challenged to prove its progressive understanding of Islam during the COVID-19 pandemic. Since March 2020, the organisation has issued religious fatwas and policies to adjust their worship and social activities during the outbreak. However, conservative elements oppose these fatwas and policies by stating that Covid-19 is a global conspiracy to destroy Islam. Through its networks and resources, Muhammadiyah keeps issuing fatwas to boost public awareness of the virus’s dangers and mortality and protect and save lives. Thus, the paper seeks to discover why and how the organisation adopts new practices in their rituals and new sites of worship and, at the same time, fights against religious ignorance and hoaxes around the Covid-19. It also seeks to determine how Muhammadiyah mobilises its networks and resources to deal with the outbreak and opposition. Finally, it examines the organisation’s relationship with state and non-state actors, nationally and internationally, to face the impacts of such a contagious virus. Drawing upon Muhammadiyah’s official fatwas, policies, statements, and socio-religious praxis, this paper finds that Muhammadiyah’s social mission, caring, and engagement during the pandemic are based on its progressive and rational belief system.