It happened just before 10 a.m. on northbound I-95 in Claymont near the Pennsylvania state line.
A car ended up on its side after going down an embankment.
Police said the female driver, approximately 40 years old, was able to communicate with first responders, but then lost consciousness.
She was taken to the hospital in critical condition.
All lanes of I-95 were reopened just before noon.
Pennsylvania State Police is investigating the crash.