The woman was hit by an F-Market train at around 5:30 p.m. near the intersection of Church and Market streets.
Police are still investigating whether she had leaned forward toward the train or if she fell off her wheelchair, but she was struck by the westbound train traveling on Market Street from Delores Street to Church Street, Officer Carlos Manfredi said.
The woman was trapped under the train.
Medics, firefighters, police and SFMTA officials arrived and used a special tool to raise the train and pull her out from under it.
She was rushed to San Francisco General Hospital suffering injuries considered life-threatening, Manfredi said.
The collision, coupled with an unrelated underground Muni outage caused by a blown transformer around the Van Ness Station tonight, snarled traffic throughout the area.
One lane of Market Street remains closed while police investigate tonight, interviewing witnesses and checking video surveillance.
