The smash happened at 6.45am Tuesday on the Bradford Road near the M1, LeedsLive reports.
A black Ford Focus, black VW Golf, and a silver Mercedes C220 were involved in the fatal incident.
The rear passengers in the Golf – two men aged 26 and 34 – were pronounced dead at the scene.
The car was driving away from the M1 towards Leeds at the time, it is understood.
One witness, Jake Ablett, said his mum was left shaken after hearing the smash and offering help.
“My mum was the first person on the scene,” he said.
“She tried to do pulse checks but it was a mess inside the car.
“She only counted four people but the airbags had gone off.
“She heard them screaming inside. She was the one who called the ambulance.
Detective Sergeant Alison Webb said: “This collision has very sadly resulted in the deaths of two men and the other occupants of the Golf are currently undergoing emergency treatment in hospital.
“We are doing everything we can to support the families of those involved at what is clearly a very difficult time for them.
“We are carrying out a comprehensive investigation to establish the full circumstances of this incident and would like to hear from anyone who witnessed either the collision itself or the movements of the vehicles involved in the time leading up to it.”