The 30-year-old skipped the winter season after a tough Olympic year in which she won bronze, and is using the event in China to prepare for the Moscow world athletics championships in August.
The Russian posted the winning height – well below her world record of 5.06 meters – at the second attempt after skipping the opening eight heights.
Up-and-coming American vaulter Mary Saxer took the silver with a personal best of 4.60 after wobbling at 4.50.
Germany’s Silke Spiegelburg, the 2011 European indoor silver medalist, won bronze with a vault of 4.55 meters.
Isinbayeva, setter of 28 world records, won gold at the Athens and Beijing Olympics but failed to defend her title in London, finishing third behind Jennifer Suhr of the United States and Cuba’s Yarisley Silva.
She remains unbeaten in five appearances in Shanghai; this being her first since 2008.