Seventeen of the charges - under Section 21(1) - relate to failing to provide and maintain, as far as reasonably practicable, a working environment that was safe and without risks to health for its employees.
Another 41 charges - under section 23 (1) - are allegations of failing to ensure, so far as was reasonably practicable, that persons other than employees were not exposed to risks to their health and safety arising from conduct of its undertaking.
Between March and July 2020, the Department of Health was responsible for the oversight and co-ordination of Operation Soteria, Victoria's first hotel quarantine program.
The state's second wave of coronavirus last year resulted in more than 18,000 new infections, 800 deaths and an 112-day lockdown.
WorkSafe alleges the department breached OHS laws by failing to appoint people with infection prevention and control expertise at the hotels it was using.
It also alleges the department failed to provide security guards with face-to-face, expert infection prevention control training and failed to provide written instruction for the use of personal protective equipment.
In all charges, WorkSafe alleges that Department of Health employees, Victorian Government Authorised Officers on secondment, or security guards were put at risk of serious illness or death through contracting COVID-19 from an infected returned traveller, another person working in the hotels or from a contaminated surface.
Each charge could result in a maximum penalty for a body corporate of $1.64 million, meaning the department faces a potential financial penalty totalling more than $95 million.
WorkSafe says the investigation into the program was complex, involving reviewing tens of thousands of documents and multiple witness interviews over 15 months.
It also reviewed material from last year's judicial inquiry, which led to the program being overhauled in December.
The program was again revamped in April, after hotel quarantine workers contracted the UK COVID-19 strain from returned travellers in February, triggering a statewide five-day lockdown.