Northern Territory police are negotiating with the detainees who are sitting outside the centre's fenced boundary, protesting peacefully, a police spokeswoman said.
The ABC has reported that the protestors are Afghan asylum seekers and not Indonesian people smugglers.
Many of the men been waiting for their cases to be processed by the Australia Federal police for up to nine months.
The protesters have unveiled a banner saying "We need protection not detention" and are reportedly demanding that their cases be dealt with.
News that makes sense
Your trusted source for staying up-to-date with the world around you. Get free daily news updates and analysis, straight to your inbox.
The ABC has reported the men broke out by pushing on one of the gates, early this morning
There are reportedly 100 to 150 police at the scene monitoring the situation.
The mass breakout follows two days of protests at the centre.
On Sunday, accused Indonesian people smugglers rioted, setting mattresses on fire and brandishing poles on the rooftop of the centre.
More than 100 detainees continued rooftop and ground protests on Monday before order was restored on Tuesday.
The Immigration Department has confirmed the breakout.
Spokesman Sandi Logan said the main concern was early morning traffic being affected by the protest.
The detention centre at the Coonawarra Naval Base currently houses 487 detainees, including 151 alleged Indonesian people smugglers.
