COVID-19 remains an ongoing public health crisis. Black Americans remain underrepresented among those vaccinated and overrepresented in both COVID-19 morbidity and mortality. Medical misinformation, specifically related to COVID-19, has exacerbated the impact of the disease in Black American communities. Communication tools and strategies to build relationships and disseminate credible and trustworthy diagnostic and preventative health information are necessary to improve outcomes and equity for historically oppressed populations. As the initial phase of a larger mixed methods project to develop, pilot, and evaluate a mobile health (mHealth) intervention among a population at high risk for COVID-19 and cardiovascular comorbidities, this study sought to explore COVID-19 information behavior among Black Americans. Specifically, this study examined (1) preferences for COVID-19 education via mHealth, (2) barriers and facilitators to COVID-19 education and diagnostic testing and routine care for associated cardiovascular and respiratory comorbidities in the local community, and (3) key content for inclusion in a COVID-19 mHealth app. This qualitative study used principles of community-based participatory research and information systems research to conduct 7 focus groups across 3 sites. Focus groups were audio recorded and transcribed for thematic analysis using an abductive approach. The study sample included 54 individuals across sites with a mean age of 50.24 (SD 11.76; range 20-71) years. Participants were primarily female (n=42, 78%) and Black (n=54, 100%) with varied education levels. Over half (n=29, 54%) of the participants were employed full-time, and nearly three-fourths (n=40, 74%) had household incomes <US $65,000. Participants used both Android (n=23, 43%) and iOS devices (n=29, 54%) and were "very comfortable" (n=37, 69%) using their mobile devices. Participants reported using a variety of sources for health information. Content-related preferences reported focus on visual presentation, user-friendly design, and privacy and highlighted the importance of community relevance, access, and community-specific content. Key barriers identified included health literacy-limiting app use, access to technology and information, and lack of trust. Increasing community relevance through community-specific messaging and the inclusion of Black providers were noted as facilitators that may increase credibility and trust. Key content identified included user-specific information such as where to get vaccines and tests, updated local COVID-19 data, travel protocols, information about long COVID-19 (post COVID-19 condition), comorbidities, frequently asked questions, and testimonials or personal stories. Increasing transparency and building trust are 2 key strategies that may improve the impact of health information messaging in Black communities. Focusing on content over context fails in the provision of critical health information and perpetuates health inequities by reinforcing systemic and structural racism. COVID-19 messaging must consider contextual information, patient needs and preferences, and patient information-seeking and information-search behaviors to establish trust and credibility, positively impact patient health outcomes, and improve health equity.