Rana M Razzaq, a security coordinator at the Memon Medical Centre, where the injured were taken, told reporters that the conductor drove the bus himself as the driver was shot dead.
The conductor, who was injured, reached the hospital with 43 bodies while two injured persons later passed away during treatment.
In the latest cold-blooded sectarian violence in Pakistan targeting the minority Shia community, six to eight bike-borne assailants opened fire indiscriminately at the bus.
The Islamic State group claimed responsibility for the grisly attack and said they gunned down 43 people.
It was the first official claim of responsibility by the IS leadership of an attack in the Afghanistan-Pakistan region.