The district attorney's office said the victims include the driver of the bus and two passengers.
The crash happened just before 8 a.m. Tuesday in the southbound lanes of the Route 1 Media Bypass near the ramp for Route 252.
Police say the bus struck the back of the trash truck and then caught fire.
Video from Chopper 6 showed the charred remains of the bus with the trash truck stopped nearby.
Chopper 6 over scene of crash on Media Bypass in Upper Providence
Police say the driver of the bus was trapped in the wreckage and died at the scene.
Passing drivers were able to pull the two passengers out of the bus through the rear door, but police say those passengers were dead when paramedics arrived.
The driver of the trash truck was taken to the hospital to be treated for minor injuries.
The bus was from Delgo, a non-profit that provides community transportation in the area.
CEO Nick Miccarelli says everyone in the organization is struggling to wrap their heads around the tragedy.
He tells Action News the driver had a clean driving record and had only been with Delgo for nine months.
"We do our best every day to provide safe rides for our clients, and today we have two clients and the driver who were killed. It's a call you never want to get," he said.
Miccarelli said his concern is for the families of those who died.
"Our hearts break for the families of the clients and for the family of our driver," he said.
The names of the victims have not been released pending family notification.