The crash happened outside The Cock Inn on Dudley Road , in Rowley Regis, at around 5pm on Thursday.
The 36-year-old male van driver suffered serious injuries and despite efforts by paramedics to save him he was pronounced dead at the scene.
Two elderly passengers on the single-decker National Express bus suffered minor injuries and were taken for treatment at Dudley's Russells Hall Hospital.
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Dudley Road was closed in both directions at the junction with Doulton Road and Springfield Lane for several hours as collision investigators examined the scene.
Det Sgt Paul Hughes, from West Midlands Police, said: "We’re currently trying to establish how this tragic incident has happened and anyone who was there, and hasn’t yet spoken to an officer, should get in touch as soon as possible.
"A road closure is in place, which may cause some disruption, however, a family has lost a loved one and we owe it to them to establish the circumstances behind this collision. Our thoughts are with them at this time."
Police said the victim's next of kin have been informed and are being supported by specialist officers.
A West Midlands Ambulance Service spokeswoman added: “Ambulance staff arrived to find a serious collision involving a van and a single-decker bus.
"The van driver, a man, was in a critical condition.
"Ambulance staff began administering emergency treatment to the man whilst working closely with fire colleagues on scene.
“The team of medics worked to administer advanced life support to the man but sadly, despite their best efforts, nothing could be done to save him, and he was confirmed dead on scene a short time later.
“Two passengers from the bus, an elderly man and woman, suffered minor injuries and were taken to Russells Hall Hospital for further checks.
" The bus driver was assessed on scene but didn’t require hospital treatment.”
A National Express West Midlands spokesperson said: "A National Express West Midlands bus was involved in an incident on Dudley Road yesterday evening.
"We are giving the police every assistance as they continue their investigation into what happened and our thoughts remain with the family and friends of the man who lost his life."
Two ambulances, two paramedic officers, HART paramedics, a BASICS emergency doctor and a Critical Care Car from the Midlands Air Ambulance attended the scene.
Anyone who saw what happened or may have dash-cam footage is asked to get in touch via the police website or by calling 101 anytime, quoting 1831 of November 7.