The transportation agency says there will be several lane closures over the next two years.
They are necessary to work on a $40-million construction project.
The expressway projects will get underway as early as Thursday night.
The first will be repairs to a 340-foot bridge that crosses Route 23 in Conshohocken.
The second and much larger project is the repair of a 6,000-foot-long I-76 viaduct that runs from about I-676 to the University Avenue exit.
At a news conference Wednesday, PennDOT's Chuck Davies said, "Both of these structures are presently on the low end of fair condition and we have to keep them from falling into poor condition."
The Conshohocken project should be completed this year.
PennDOT said the viaduct project will take two summers.
On an average day, 130,000 vehicles use the elevated stretch of highway which runs near 30th Street Station.
This year's work will involve eastbound lanes. Next year, the work will shift to westbound lanes.
For this year, the expectation is on many weekday nights and weekend days there will be a single cattle chute eastbound.
On 10 weekends this season, all eastbound lanes will be shut down during nighttime hours, along with some nearby ramps. The nighttime weekend shutdowns are expected to begin in June. The exact dates have not been announced.
During those nighttime shutdowns, crews will repair and replace the damaged structure and road surfaces.
PennDOT's district executive for this area, Ken McClain, urged drivers to be prepared for delays and to be ready to take detours during active construction times.
McClain added, "We would just encourage people that if they don't have to use the Schuylkill Expressway during the construction to please avoid it at all costs."
PennDOT suggests drivers who do venture into the work zones to consult traffic apps like Waze or go to the special PennDOT website I76viaduct.com for the latest information.