MFB deemed the fire under control as of 4.49pm.
Asbestos was found in the roof structure after hundreds were evacuated earlier this afternoon.
Earlier flames spread to the roof, despite efforts from firefighters using an aerial hose to cool the area.
Fire fighters were called to the Harbour Esplanade venue to extinguish the blaze — which sent thick smoke billowing across the inner city just before 3pm.
Two managers are being treated for smoke inhalation.
The location of the building on central pier made access by the fire brigade difficult.
Crews worked to ensure the blaze didn’t spread to other restaurants and shops in the precinct.
Witnesses say the evacuation by staff was swift and professional.
It is believed the fire started in a kitchen ventilation system at the venue, opposite Etihad Stadium and AFL House, just before 3pm.
MFB assistant chief fire officer Darren McQuade said asbestos had been found in the building’s roof structure.
“Precautions have been implemented to minimise contamination,” he said.
All occupants have been accounted for and only two people have been treated by ambulance for minor smoke inhalation.
About 200 staff and patrons were evacuated.
There are 15 fire trucks, 50 fire fighters and one fire boat on scene.
A fire boat was providing support from the water.
Smoke billows from the pub. Picture: Matthew Hackling.
Police have cordoned off the area while traffic on Harbour Esplanade has come to a standstill.
Assistant chief fire officer Darren McQuade said people should stay clear of the area.
“We’ve sent an advice notice out to the community asking them to keep clear of the area, saying there is a fire in the area and also that there is smoke in the area and they shouldn’t be concerned, that the fire fighters are working hard to extinguish the flames,” he said.