The COVID-19 pandemic introduced significant novel risks for healthcare workers and healthcare services. This study aimed to determine the prevalence, trends, characteristics, and sources of COVID-19 infection among healthcare workers during the early COVID-19 pandemic in Malaysian hospitals. A cross-sectional study used secondary data collected from a COVID-19 surveillance system for healthcare workers between January and December 2020. Two surges in COVID-19 cases among healthcare workers in Malaysia were epidemiologically correlated to a similarly intense COVID-19 pattern of transmission in the community. The period prevalence of COVID-19 infection and the mortality rate among healthcare workers in Malaysia were 1.03% and 0.0019%, respectively. The majority of infections originated from the workplace (53.3%); a total of 36.3% occurred among staff; a total of 17.0% occurred between patients and staff; and 43.2% originated from the community. Healthcare workers had a 2.9 times higher incidence risk ratio for the acquisition of COVID-19 infection than the general population. Nursing professionals were the most highly infected occupational group (40.5%), followed by medical doctors and specialists (24.1%), and healthcare assistants (9.7%). The top three departments registering COVID-19 infections were the medical department (23.3%), the emergency department (17.7%), and hospital administration and governance (9.1%). Occupational safety and health units need to be vigilant for the early detection of a disease outbreak to prevent the avoidable spread of disease in high-risk settings. The transformation of some tertiary hospitals to dedicated COVID-19 care, the monitoring of new procedures for the management of COVID-19 patients, and appropriate resource allocation are key to successful risk mitigation strategies.