The highway opened up shortly after 12 noon after being closed for several hours Sunday morning.
The crash happened around 3:45 a.m. near Pennsylvania Avenue just before the toll bridge to New Jersey.
One victim was ejected from a vehicle and pronounced dead on the highway.
Two other victims were taken to Aria-Hospital Bucks County and St. Mary's Hospital. No word on their conditions.
Rescue crews used dogs to search under Route 1 for another possible victim who was thrown from a vehicle into a wooded area. No word if a fourth victim was ever found.
While Route 1 was closed, traffic was directed onto Route 13.
So far no word what sparked the crash or the identies of the victims.