The crash occurred in O’Brien Street at Mount Druitt about 9.50pm yesterday.
One of the drivers had to be freed from the wreckage by fire crews after he became trapped inside his vehicle.
He was treated by paramedics before being taken to Westmead Hospital in a serious but stable condition.
The second driver was uninjured and is assisting police.
Anyone with dashcam is urged to contact Mount Druitt Police or Crime Stoppers on 1800 333 000.