The four, who were all travelling in the same coach, are understood to have been part of the trip for families from Newcastle to Flamingo Land theme park and zoo near Malton.
It is thought one of the coaches crashed into a car travelling in front of it, and the second coach is then thought to have hit the back of the first.
Around 18 others received medical checks after the accident which happened just before 11.30am on Saturday, on the A170 near Pickering in North Yorkshire.
A spokeswoman for the Yorkshire Ambulance Service confirmed there were a "number of walking wounded" and several people had been checked over by a doctor at the scene but did not require hospital treatment.
She added: "It appears most people had a lucky escape. The two adults and two children have serious injuries and have been taken to hospital but their condition is not believed to be life-threatening."
It was reported that up to 100 people were travelling on the coaches.
The road was closed in both directions while emergency services dealt with the accident but reopened at around 3pm.