The COVID-19 pandemic has profoundly affected life worldwide. Governments have been faced with the formidable task of implementing public health measures, such as social distancing, quarantines, and lockdowns, while simultaneously supporting a sluggish economy and stimulating research and development (R&D) for the pandemic. Catalyzing bottom-up entrepreneurship is one method to achieve this. Home-grown efforts by citizens wishing to contribute their time and resources to help have sprouted organically, with ideas shared widely on the internet. We outline a framework for structured, crowdsourced innovation that facilitates collaboration to tackle real, contextualized problems. This is exemplified by a series of virtual hackathon events attracting over 9000 applicants from 142 countries and 49 states. A hackathon is an event that convenes diverse individuals to crowdsource solutions around a core set of predetermined challenges in a limited amount of time. A consortium of over 100 partners from across the healthcare spectrum and beyond defined challenges and supported teams after the event, resulting in the continuation of at least 25% of all teams post-event. Grassroots entrepreneurship can stimulate economic growth while contributing to broader R&D efforts to confront public health emergencies.