Double demerits will apply on NSW roads from Friday until the end of Monday in a bid to slow down drivers over the long weekend.
Thousands of people are expected to take advantage of the warm spring weather and eased COVID-19 restrictions to drive into the regions.
Police and Emergency Services David Elliott said police would be out in force across the state for Operation Slowdown.
"One road fatality is one too many. Stick to the speed limit, put your phone down, and observe the road rules. We want people to arrive at their destination safely," Mr Elliott said on Wednesday.
Regional Transport and Roads Minister Paul Toole said authorities expected a lot of people to travel to the regions.
"We are asking everyone to plan your trip in advance, allow plenty of extra travel and be patient on the roads," he said.
"Over the 2019 October long weekend we tragically lost six people on our roads. That is six people too many."
The long weekend coincides with the start of the boating season and specialist Marine Area Command officers will conduct random breath testing and mobile drug testing operations, as well as boat inspections.
Police Commissioner Michael Fuller said police will target speeding, drink and drug driving, driving while fatigued, mobile phone, helmet and other traffic offences.
"The message is clear - don't speed or drive under the influence of drugs or alcohol on the roads and waterways, and importantly use safety equipment, such as seat belts and life jackets because we know they really do save lives."
Australian Associated Press