The rider, on a lime green bicycle, and the National Express West Midlands bus crashed in Bloxwich Road, Bloxwich, just before 4pm on Thursday.
A large cordon was set up in the road after the bike became stuck underneath the bus, which had sustained a smashed windscreen.
The cyclist's clothing could also be seen on the road behind the bus.
Ambulance crews, critical care paramedics and doctors from West Midlands Ambulance Service and Midlands Air Ambulance were called to the scene to administer "advanced trauma care" to the cyclist.
A West Midlands Ambulance Service spokeswoman said: “Crews arrived at the scene to find the cyclist, a man, in a serious condition with potentially life changing injuries.
“Staff administered advanced trauma care to the man, and he was conveyed to Queen Elizabeth Hospital on blue lights and sirens for further treatment. The West Midlands CARE Team and Midlands Air Ambulance crew travelled onboard, continuing with treatment on route."
On Thursday evening a spokesperson from West Midlands Police said: "Bloxwich Road is currently closed at the junction of Northumberland Way after a collision between a cyclist and a bus just before 4pm today.
"The cyclist has suffered serious injuries."
The bus driver was discharged at the scene.