Background: Monitoring differences in COVID-19 vaccination uptake in different groups is crucial to help inform the policy response to the pandemic. A key data gap is the absence of data on uptake by occupation. This study investigates differences in vaccination rates by occupation in England, using nationwide population-level data. Methods: We calculated the proportion of people who had received three COVID-19 vaccinations (assessed on 28 February 2022) by detailed occupational categories in adults aged 18–64 and estimated adjusted ORs to examine whether these differences were driven by occupation or other factors, such as education. We also examined whether vaccination rates differed by ability to work from home. Results: Our study population included 15 456 651 adults aged 18–64 years. Vaccination rates differed markedly by occupation, being higher in health professionals (84.7%) and teaching and other educational professionals (83.6%) and lowest in people working in elementary trades and related occupations (57.6%). We found substantial differences in vaccination rates looking at finer occupational groups. Adjusting for other factors likely to be linked to occupation and vaccination, such as education, did not substantially alter the results. Vaccination rates were associated with ability to work from home, the rate being higher in occupations which can be done from home. Many occupations with low vaccination rates also involved contact with the public or with vulnerable people. Conclusions: Increasing vaccination coverage in occupations with low vaccination rates is crucial to help protecting the public and control infection. Efforts should be made to increase vaccination rates in occupations that cannot be done from home and involve contact with the public.