On March 24, 2020, the South Dakota Department of Health (SDDOH) was notified of a case of coronavirus disease 2019 (COVID-19) in an employee at a meat processing facility (facility A) and initiated an investigation to isolate the employee and identify and quarantine contacts. On April 2, when 19 cases had been confirmed among facility A employees, enhanced testing for SARS-CoV-2, the virus that causes COVID-19, was implemented, so that any employee with a COVID-19-compatible sign or symptom (e.g., fever, cough, or shortness of breath) could receive a test from a local health care facility. By April 11, 369 COVID-19 cases had been confirmed among facility A employees; on April 12, facility A began a phased closure* and did not reopen during the period of investigation (March 16-April 25, 2020). At the request of SDDOH, a CDC team arrived on April 15 to assist with the investigation. During March 16-April 25, a total of 929 (25.6%) laboratory-confirmed COVID-19 cases were diagnosed among 3,635 facility A employees. At the outbreak's peak, an average of 67 cases per day occurred. An additional 210 (8.7%) cases were identified among 2,403 contacts of employees with diagnosed COVID-19. Overall, 48 COVID-19 patients were hospitalized, including 39 employees and nine contacts. Two employees died; no contacts died. Attack rates were highest among department-groups where employees tended to work in proximity (i.e., <6 feet [2 meters]) to one another on the production line. Cases among employees and their contacts declined to approximately 10 per day within 7 days of facility closure. SARS-CoV-2 can spread rapidly in meat processing facilities because of the close proximity of workstations and prolonged contact between employees (1,2). Facilities can reduce this risk by implementing a robust mitigation program, including engineering and administrative controls, consistent with published guidelines (1).