Little is known about occupational SARS-CoV-2 exposures and COVID-19 outcomes. We established a Doctor’s First Reports of Occupational Injury or Illness (DFR)-based surveillance system to study cases of work-related COVID-19 exposures and disease. The surveillance data included demographics, occupation, industry, exposure, and illness, details including hospitalization and lost work. We classified workers into ‘healthcare’, non-healthcare ‘public-facing’, or ‘other’ worker groups, and rural–urban commuting areas (RUCAs). We describe worker exposures and outcomes overall by worker group and RUCA. We analyzed 2848 COVID-19 DFRs representing workers in 22 detailed occupation groups and 19 industry groups. Most DFRs were for workers in metropolitan RUCAs (89%) and those in healthcare (42%) and public-facing (24%) worker groups. While DFRs were from 382 unique worksites, 52% were from four hospitals and one prison. Among 1063 DFRs with a suspected exposure, 73% suspected exposure to a patient or client. Few DFRs indicated hospitalization (3.9%); however, the proportion hospitalized was higher among nonmetropolitan (7.4%) and public-facing (6.7%) workers. While 56% of DFRs indicated some lost work time, the proportion was highest among public-facing (80%) workers. Healthcare and prison workers were the majority of reported occupational COVID-19 exposures and illnesses. The risk of COVID-19 hospitalization and lost work may be highest among nonmetropolitan and public-facing workers.