An early-morning police chase has ended with a man wanted over alleged domestic violence ejected from his car and fighting for his life in a Sydney hospital.

The incident began after officers approached a red Mazda hatchback parked on the Great Western Highway in Bowenfels about 5am today, but the car drove away.

Officers scoured the area and spotted it on Werriway Street in South Littleton about two hours later.

The Mazda allegedly rammed a police car and drove at an officer.

No one was injured, and the car continued to the Bells Line of Road, where police began a pursuit.

It was later terminated due to the allegedly dangerous driving. 

The Mazda travelled towards Faulconbridge, where a second pursuit was initiated and again terminated a short time later due to safety concerns.

A police helicopter and officers tracked the car to Penrith, where spikes were deployed on Castlereagh and Cranebrook Road.

The car continued driving and crashed into a Toyota SUV, a Sprinter van and a Hyundai.

The driver of the Mazda, a 33-year-old man, was ejected from the car and arrested a short distance away.

He was treated by paramedics for serious head injuries before being taken to Westmead Hospital in a critical condition.

Police investigations found the man had been wanted on two outstanding warrants for domestic violence-related offences.

The driver of the SUV, a 35-year-old man, suffered minor hand injuries. All the other drivers were assessed by paramedics and were uninjured.

A crime scene has been established and a critical incident has been declared.

The investigation will be independently reviewed by the Professional Standards Command with oversight by the Law Enforcement Conduct Commission.