Objective: To examine factors associated with COVID-19 vaccine uptake in a sample of Latino/a/x sexual and/or gender minority (SGM) individuals in South Florida. Design: Data were collected via an online survey from March 2021 to August 2022, as part of the Community Engagement Alliance Against COVID-19 Disparities. A multivariate regression analysis was fit using completion of a COVID-19 vaccine regimen as the outcome. Key covariates included trusted sources of information (eg, doctor, media), COVID-19–related challenges (eg, accessing medication, transportation), and dominant wave of SARS-CoV-2 at the time of data collection. Setting: Miami-Dade and Broward counties, Florida. Results: White Latino/a/x, bachelor's educated respondents, and those with high levels of trust in community organizations had significantly greater odds of vaccination. Conclusion: Community organizations may be key to improving vaccine uptake among marginalized Latino/a/x SGM for COVID-19 and other emerging communicable diseases, such as meningitis and Mpox (monkeypox). The results of this study suggest that tailored public health messaging and additional funding for vaccine distribution are needed to better equip community organizations with the resources they need to serve this population.