Background: Telehealth has been increasingly adopted by health care systems since the start of the COVID-19 pandemic. Although telehealth may provide convenience for patients and clinicians, there are several barriers to accessing it and using it effectively to provide high-quality patient care. Objective: This study was part of a larger multisite community-engaged study conducted to understand the impact of COVID-19 on diverse communities. The work described here explored the perceptions of and experience with telehealth use among diverse and underserved community members during COVID-19. Methods: We used mixed methods across three regions in the United States (Midwest, Arizona, and Florida) from January to November 2021. We promoted our study through social media and community partnerships, disseminating flyers in English and Spanish. We developed a moderator guide and conducted focus groups in English and Spanish, mostly using a videoconferencing platform. Participants were placed in focus groups with others who shared similar demographic attributes and geographic location. Focus groups were audio-recorded and transcribed. We analyzed our qualitative data using the framework analytic approach. We developed our broader survey using validated scales and with input from community and scientific leaders, which was then distributed through social media in both English and Spanish. We included a previously published questionnaire that had been used to assess perceptions about telehealth among patients with HIV. We analyzed our quantitative data using SAS software and standard statistical approaches. We examined the effect of region, age, ethnicity/race, and education on the use and perceptions of telehealth. Results: We included data from 47 focus groups. Owing to our mode of dissemination, we were not able to calculate a response rate for the survey. However, we received 3447 English-language and 146 Spanish-language responses. Over 90% of participants had internet access and 94% had used telehealth. Approximately half of all participants agreed or strongly agreed that telehealth would be beneficial in the future because it better fit their schedules and they would not need to travel. However, approximately half of the participants also agreed or strongly agreed they would not be able to express themselves well and could not be examined when using telehealth. Indigenous participants were especially concerned about these issues when compared to other racial groups. Conclusions: This work describes findings from a mixed methods community-engaged research study about telehealth, including perceived benefits and concerns. Although participants enjoyed the benefits of telehealth (eg, not having to travel and easier scheduling), they also had concerns (eg, not being able to express themselves well and not having a physical exam) about telehealth. These sentiments were especially notable among the Indigenous population. Our work highlights the importance of fully understanding the impact of these novel health delivery modalities on the patient experience and actual or perceived quality of care received.