The female driver of the Kia was taken to Waikato Hospital by ambulance with moderate injuries including broken bones. Her male passenger was able to walk with minor injuries.
The family had been heading home to Auckland.
A nearby resident woken by the crash said it was loud.
When she looked out the window, she saw the two SUVs on their side and the trailer, which had a vehicle on board, was also tipped over.
She said several trucks had already pulled over to offer assistance and witnesses had said the SUV and trailer had been seen fishtailing for some time before the crash.
The Kia appeared to have spun around and was facing in the opposite direction.
Acting Waikato district road policing manager Senior Sergeant Jeff Penno said the Toyota appeared to have veered off one side of the road which may have caused the fishtailing as the driver tried to get the vehicle back to the left side of the road.
Mr Penno said the severity of the injuries would have been lessened if the young children had been in car seats.
"The point we are making is the children weren't in car seats.
"Why would you do that to your children? Why would you put your most prized possession in danger like that?
"You never know what is around the next corner, you never know if there's going to be a fault with the vehicles and that's why we have seatbelts, airbags and ABS brakes. They are all there to make you safe and ignoring those rules is simply beyond belief."
Westpac Waikato Air Ambulance pilot Dan Harcourt said a 5-year-old boy suffered a serious left arm injury and possible internal injuries and was flown with his father, who suffered minor cuts and abrasions, to the Starship hospital.
The younger brother suffered a head injury, and was flown with his mother, who also had cuts and abrasions, to the Starship in the Auckland Westpac Helicopter.
The road, which runs parallel to SH1 between Auckland and Hamilton, was closed for six hours while the serious crash unit investigated.
