It happened around midnight on Street Road near the I-95 interchange in Bensalem Township.
The high-speed collision was so powerful that one of the three cars involved caught fire.
Bensalem police say when they arrived on the scene, they found a silver 2013 Chevrolet Sonic fully engulfed in flames.
The driver had been ejected from the vehicle and was pronounced dead at the scene. He has been identified as 44-year-old Timur Khabelov from Brooklyn, New York.
Two other passengers were rescued from inside the burning vehicle and transported to Jefferson Torresdale Hospital in critical condition.
They have been identified as 43-year-old Farruh Homidov and 39-year-old Askar Narziev.
The drivers of the other two vehicles, a 2017 Dodge Journey and a 2015 Honda Accord, were both transported to area hospitals with non-life-threatening injuries.
Their identities have not been released.
"It's one person that decided to drive his car at a high rate of speed and just disregard all traffic signals," said Detective Sgt. Glenn Vandegrift. "It never would have happened if this driver had been obeying the law, and traveling the speed limit, and stopping for red lights. It's that simple."
Bensalem police say traffic cameras show Khabelov was driving at a high rate of speed eastbound on Street Road when he ran a red light and struck the Dodge Journey.
Khabelov's vehicle then went airborne, crossed the center median, and struck the Honda Accord before bursting into flames.
"This caused chaos for everybody involved. I do want to say that I do feel for the family of the deceased driver. He made some bad decisions, unfortunately, and there are some other people paying for it," said Det. Sgt. Vandegrift.
Police say they have not ruled out the involvement of drugs or alcohol in the crash, pending an autopsy and toxicology reports.
The crash remains under investigation.