COVID-19 vaccine hesitancy threatens pandemic control efforts. We evaluated vaccine hesitancy in the US by employment status and occupation category during the COVID-19 vaccine rollout. US adults 18-64 years completed an online COVID-19 survey 3,179,174 times from January 6-May 19, 2021. Data was aggregated by month. Survey weights matched the sample to the US population age, gender, and state profile. Weighted percentages and 95% confidence intervals (CI) were calculated. Changes in vaccine hesitancy from January-May varied widely by employment status (e.g., -7.8% [95%CI, -8.2--7.5] among those working outside the home, a 26.6% decrease; -13.3% [95%CI, -13.7--13.0] among those not working for pay, a 44.9% decrease), and occupation category (e.g., -15.9% [95%CI, -17.7--14.2] in production, a 39.3% decrease; -1.4% [95%CI, -3.8--1.0] in construction/extraction, a 3.0% decrease). April 20-May 19, 2021, vaccine hesitancy ranged from 7.3% (95%CI, 6.7-7.8) in computer/mathematical professions to 45.2% (95%CI, 43.2-46.8) in construction/extraction. Hesitancy was 9.0% (95%CI, 8.6-9.3) among educators and 14.5% (95%CI, 14.0-15.0) among healthcare practitioners/technicians. While the prevalence of reasons for hesitancy differed by occupation, over half of employed hesitant participants reported concern about side effects (51.7%) and not trusting COVID-19 vaccines (51.3%), whereas only 15.0%) didn’t like vaccines in general. Over a third didn’t believe they needed the vaccine, didn’t trust the government, and/or were waiting to see if it was safe. In this massive national survey of adults 18-64 years, vaccine hesitancy varied widely by occupation. Reasons for hesitancy indicate messaging about safety and addressing trust are paramount.