The crash in the 300 block of East H Street, near the Interstate 805 ramp, was reported just before 3:20 a.m., according to Chula Vista police.
A woman in her car and a man in his were apparently racing when the crash occurred, sending the woman's vehicle into a tree in the center median, police said in a statement.
Her car was "almost completely wrapped around'' the tree and firefighters had to cut her out of the vehicle, police said, adding that she was then flown to an area hospital with serious injuries.
The uninjured man's car came to rest in westbound lanes and had only minor damage, police said, adding that he was arrested at the scene and booked into county jail on suspicion of various crimes related to racing and operating a motor vehicle while under the influence.
Police estimated traffic in the area would be affected until at least 9 a.m.