The terrifying ordeal happened Monday inside a home on the 500 block of East Clarkson Avenue in the city's Olney section.
Police say a 51-year-old woman and a 39-year-old man were inside when they heard a commotion at the back door.
When the victims attempted to run upstairs, two unknown males came into the basement and fired one shot, striking the woman in the head as she tried to run upstairs.
She was rushed to Einstein Medical Center and listed in critical condition.
The man inside the home was not injured, officials say.
The suspects were said to have fled the scene in different directions.
Police later released a video of one of the alleged shooters who was caught on store surveillance video a day before the incident.
Anyone with information is asked to contact police.