The State Emergency Service has ordered anyone from Condong to Tumbulgum and surrounding areas to leave via the Tweed Valley Way.
An SES spokesperson said the region has been deemed "a high danger area" and about 1000 properties are affected.
The order comes after the Tweed River burst its banks near Tumbulgum on Tuesday, with minor flooding in the area. Flash flooding has closed roads and isolated small communities.
The SES says electricity, phones, internet, water and sewerage could be interrupted, and people in those areas need to closely monitor the weather and road closures.
Energy provider, Essential Energy, says more than 700 homes from Kempsey to the Queensland border are without power and crews are working to restore services, although flooding is restricting access to 120 homes.
The SES says residents should monitor the rapidly changing situation in NSW.
Earlier an SES spokesperson said "around 1000 homes in the Murwillumbah area are potentially affected".
It warns once floodwater begins inundating the area, roads may be cut, trapping anyone who stays behind.
"If you remain in the area after this time, you may become trapped and it may be too dangerous for NSW SES to rescue you," the SES warned in a statement on Tuesday.
The Bureau of Meteorology says some of the rainfalls are expected to be record breaking.
Several locations across the Tweed catchment received more than 500mm of rain in the last four days.
The BOM says 578mm has fallen at Terania Creek on the NSW mid-north coast since Friday.
Meteorologist Helen Reid said "we'll be looking to the data base, with some places expected to break new records".
One of the heaviest falls in the past 24 hours was recorded at Bellingen on the mid-north coast of NSW, where 251mm fell in the 24-hours until 9am on Tuesday.
The BOM says the system is moving further south with heavy rainfall now expected on the mid-north coast between Grafton and Taree, and some areas expecting up to 150mm in the next 24 hours.
NSW Premier Gladys Berejiklian said weather experts had warned La Nina would have an impact all over over Australia.
"So we need to expect the unexpected," she told ABC TV.
"I'm hoping what we've seen in the last few days won't be repeated frequently over summer, but it could. Our weather experts tell us we're expecting conditions worse than what we've seen in quite a number of years."
NSW SES Assistant Commissioner Nicole Hogan said there had been more than 1000 calls for help in the past few days.
"There are no evacuations taking place at the moment. It is a warning for the community so that they can prepare to evacuate should the situation arise," she told ABC TV.
"There was significant rainfall within the Tweed area last night. We've also had significant weather in Coffs Harbour and Lismore."
The low-pressure system off the coast of southeast Queensland has brought massive rainfall and gale-force winds, which combined with king tides to wash away much of Byron Bay's Main Beach on Monday.
On the Gold Coast the weather system has also caused massive erosion, with the surf club at Currumbin becoming an island.
A team of 300 SES workers from across the state had been sent to support the northern NSW teams, as well as resources from Fire & Rescue, NSW RFS and NSW Police to support of the operation.
Queensland Fire and Emergency Services deputy commissioner Mark Roche said his crews had received about 1400 requests for help - mainly for leaking roofs and tarping and downed trees.
The wind and heavy rain was expected to ease, but he urged people to remain vigilant, stay out of floodwaters, drive with caution and turn back if they see a road or a bridge that's flooded.
"As we say, if it's flooded, forget it," he told ABC TV.