Local councilwoman Sherin Akhtar said in a post on X that the bus was headed to West Kirby Grammar School at the time.
The incident "involving the W3 bus service" was reported to West Kirby Grammar as being known to them.
The school stated, "We are in contact with the bus company and emergency agencies, who have instructed that they will keep us updated.
We need your assistance to keep our phone lines open so that we can continue this conversation.
As part of the emergency response between junction 4 in Bebington and junction 5 in Hooton, two air ambulances were dispatched to the scene.
One female patient has already been sent to the hospital with serious trauma-related injuries, according to the ambulance service, which has declared a major emergency.
Nearly 50 additional people are also being evaluated on the site.
To transport individuals away from the location, "we are working closely with our incident partners."
Health care professionals participating in industrial action, according to Unison, returned to work right away to assist in the aftermath of the tragedy.
"My thoughts are with everyone who has been affected by the terrible incident on the M53," wrote Mick Whitley, the Labour MP for Birkenhead, in a post on the social media platform X.
"Please stay away from the area so that the emergency personnel can perform their duties.
"If you are a Birkenhead constituent who has suffered, I will support you in any way I can."