State Highway 1 at Karapiro is not likely to reopen until about 6pm after a truck carrying volatile chemicals rolled.
The crash happened between Kentucky and Maungatautari Rds at about 10.10am.
Waikato fire area commander Roy Breeze said they had identified the seven chemicals on board - a variety of hazardous acids - and had just begun a meticulous clean-up.
One barrel had created a "minor" spill.
Six fire crews are at the scene, along with a Hazmat unit, which is using a digger and forklift to lift the containers from the truck.
Onboard are about 15 200-litre containers containing corrosive material, and a couple of 1000-litre containers, as well smaller bits and pieces.
"The only way we can deal to it is by slowly unloading it," Breeze said.
"It's a bit like pick-up sticks at the moment. You move one thing, and the other thing falls over."
The biggest issue was making sure the chemicals didn't mix.
"The containers have really stood up to the crash quite well. We've just come across a very minor leak and we're just going to keep puttering along and hopefully it will stay like that until we've unloaded it."
Sand had also been placed around the crash scene to soak up any leakage.
He didn't believe acid had got into any waterways, the main leak at this stage was the truck's hydraulic fluid.
Breeze estimated the road would be open by 5pm or 6pm.
"It will really depend on what we come across. We're only a quarter of the way into the truck now and so if it's leaking up the front it's going to change the whole ball game."
He said it was a "very labour-intensive" exercise, as each container had to be dealt with carefully.
Earlier, Waikato police Senior Sergeant Phil Ruddell said the road closure would depend on what chemicals were being transported.
There are chemicals on board "that by themselves are not problematic but if they are mixed together they may cause problems", Ruddell said.
Northern fire communications shift manager Daniel Nicholson said they had identified seven chemicals on board the truck.
Some had spilled but there didn't appear to be any immediate danger to firefighters, who were dressed in level-three protective suits, he said.
Crews were still investigating the crash and working out the best way to tidy the scene. It's unclear how long the road will be closed.
Diversions are in place via Karapiro Rd and Taotaoroa Rd.
The truck driver suffered minor injuries.