SEPTA Transit Police said the woman got onto the bus around 7 p.m., when it was filled with passengers.
Police said the woman, believed to be in her 30s, targeted one person on the bus who was sitting next to her.
SEPTA police said the suspect was caught on camera striking the 69-year-old victim in the nose.
Authorities said the woman first got on a Route 70 bus outside Curran-Fromhold Correctional Facility on State Road.
It's unclear if the two women exchanged words, but SEPTA police said the suspect suddenly struck the older woman and then got off at the next stop at Bustleton and Cottman.
Police said the victim was badly injured and taken to the hospital.
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"Fights happen on the bus, but I think it's a little different when you see a person that's elderly," said Lt. Michael Wright, with SEPTA Transit police. "As you see on the video it appears to be an assault, and makes us turn it up a notch, to try to figure out what happened because that person can't even defend themselves."
Police believe the women never met each other before.
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There's no audio on the video so police can't tell if anything was said before the strike.
Police are asking for witnesses to come forward. Anyone with any information is asked to contact SEPTA Transit Police.