Brown floodwater gushing down the Brisbane River has already caused banks to burst, and water flow is expected to peak over the course of tomorrow (Jan. 13).
The river is expected to rise beyond a record level recorded in 1974 that broke its banks, flooding more than 6,000 homes and killing 14 people, according to CNN.
While the majority of Brisbane's population in the city's hilly suburbs will remain safe from the floodwaters, thousands of properties in low-lying areas are likely to be affected.
Queensland Premier Anna Bligh reportedly said: "We are preparing for the worst natural disaster in our history."
Heavy rainfall over much of Northeast Australia has already wreaked major havoc and devastated smaller towns and villages, including Rockhampton and Toowoomba.
Latest reports show that at least 12 people are known to have died and 43 are missing, according to Sky News.
Australia's Prime Minister Julia Gillard told the news channel: "People do have to be prepared for the death toll to rise."