Physicians are on the frontline of the COVID-19 pandemic with responsibility to manage the disease. The aim of this study is to investigate physicians’ knowledge, attitudes, and preventative practices regarding the COVID-19 pandemic and COVID-19 vaccinations, as well as explore physicians’ recommendations for future pandemics. A mixed-methods online survey was disseminated to physicians globally. The survey was distributed via social media from August 9–30, 2021. Data collected included sociodemographic characteristics, knowledge, attitudes, and practices towards COVID-19, concerns regarding vaccinations, and perspectives on policies implemented. Descriptive statistics were reported, and qualitative data were analysed using inductive thematic analysis. A total of 399 physicians from 62 countries completed the survey, with similar participation from High Income Countries and Low- or Middle-Income Countries. Most physicians (87%) revealed a good level of knowledge while only half (54%) reported adhering to adequate preventative measures. More than half of participants (56%) indicated that the policies implemented to handle COVID-19 by their public health agencies were insufficient or disorganised. While most physicians reported increased mental stress (61%) and described their experience with COVID-19 using negative terminology (63%), the majority of physicians (87%) indicated they are willing to continue working in healthcare. Physicians globally possessed good knowledge of COVID-19 and vaccinations; yet improvements in ensuring compliance with preventative practices is warranted. Findings from this study have important implications. As recommended by physicians, efforts to manage pandemics should involve (1) strengthening health systems, (2) minimising adverse effects of infodemics, (3) delegating decision-making roles appropriately, and (4) acknowledging global responsibility.