Background The unprecedented rapid development of COVID-19 vaccines has faced SARS-CoV- (COVID-19) vaccine hesitancy, which is partially fueled by the misinformation and conspiracy theories propagated by anti-vaccine groups on social media. Research is needed to better understand the early COVID-19 anti-vaccine activities on social media. Methods This study chronicles the social media posts concerning COVID-19 and COVID-19 vaccines by leading anti-vaccine groups (Dr Tenpenny on Vaccines, the National Vaccine Information Center [NVIC] the Vaccination Information Network [VINE]) and Vaccine Machine in the early months of the COVID-19 pandemic (February–May 2020). Results Analysis of 2060 Facebook posts showed that anti-vaccine groups were discussing COVID-19 in the first week of February 2020 and were specifically discussing COVID-19 vaccines by mid-February 2020. COVID-19 posts by NVIC were more widely disseminated and showed greater influence than non-COVID-19 posts. Early COVID-19 posts concerned mistrust of vaccine safety and conspiracy theories. Conclusion Major anti-vaccine groups were sowing seeds of doubt on Facebook weeks before the US government launched its vaccine development program 'Operation Warp Speed'. Early anti-vaccine misinformation campaigns outpaced public health messaging and hampered the rollout of COVID-19 vaccines.