Introduction The COVID-19 pandemic has changed the working environment for general practitioners (GPs). GPs had to adapt quickly when care mitigation for mild COVID-19 in the community began. We assessed Malaysian GPs' knowledge and preparedness to manage COVID-19. Method A cross-sectional online survey was conducted between May and October 2022 among the GPs. Emails were sent to GPs affiliated with the main GP organizations in Malaysia, such as the Academy of Family Physicians of Malaysia (AFPM). Additionally, participation was sought through social media groups, including the Association of Malaysian Islamic Doctors, the Federation of Private Medical Practitioners' Associations Malaysia, and the Primary Care Network. Data was collected using a self-administered questionnaire on items related to knowledge and preparedness to manage COVID-19. The content was validated by six experts. Multiple logistic regression was used to determine the predictors for preparedness. Results A total of 178 GPs participated in this study. The mean age of the GPs was 41.8 (SD 12.37) years, 54.5% were males, 47.8% had a postgraduate qualification, and 68% had up to 10 years of general practice experience. Their practices are commonly solo (55.1%), located within an urban area (56.2%) and 47.2% operate 7 days a week. A majority of GPs (n = 124, 69.7%) had a good level of knowledge of COVID-19. In contrast, about a third (n = 60, 33.7%) had a good level of preparedness to manage COVID-19. GPs with a good level of knowledge of COVID-19 had 1.96 times the odds of having a good level of preparedness as compared to GPs with lower knowledge (OR = 2.11 (95% CI: 1.06, 4.18, p = 0.03)). Conclusion A good level of knowledge is a predictor for preparedness to manage COVID-19. Relevant and targeted measures to enhance knowledge for better preparedness among the GPs to respond to future pandemics are needed.