(1) Background: In Brazil, the first case of the novel coronavirus occurred on the 25 February 2020, and since then, it has spread rapidly over the entire country. During a pandemic, knowledge, attitudes, and practices are expected to largely influence the adherence to non-pharmacological interventions (NPIs). We evaluated the knowledge about COVID-19 and associated factors early in the outbreak among the Brazilian population. (2) Methods: A Brazilian cross-sectional study was carried out using an online questionnaire. The questionnaire consisted of the following topics: isolation, caring for someone sick at home, cleaning habits, disinfecting habits, and true and fake news. Logistic regression was conducted using sociodemographic and associated factors as the independent variables and a knowledge score as the dependent variable to estimate factors associated with knowledge about COVID-19. Crude, sex-, and age-adjusted odds ratios (OR) were calculated. (3) Results: Participants with a better educational status had higher odds of having a higher knowledge score (OR = 2.49, 95% CI = 1.15–5.37). Similarly, healthcare providers (health students and professionals) had higher odds of having higher scores regarding knowledge about COVID-19 (OR = 1.62, 95% CI = 1.05–2.48) than other counterparts. Of the wrong answers, the most frequent was the isolation period, followed by household recommendations to prevent COVID-19 and cleaning habits. (4) Conclusions: In conclusion, our study suggests that a higher educational status and being a healthcare provider are conditions associated with superior knowledge about COVID-19. In addition, inadequate knowledge related to isolation, COVID-19 prevention, and cleaning habits were found in our study. We believe that improving awareness to address these specific COVID-19 issues through a health education campaign is a significant approach for public health policymakers to fight against COVID-19 in Brazil.