The incident happened just after 3.30pm on the eastbound carriageway between junction 10 and junction 8 and 9 when a Ford Mondeo collided with a Mazda.
The male driver of the Ford Mondeo was thrown out of his car and rushed to Wexham Park Hospital in Slough while a fire crew from Wokingham Road and police officers cleared the scene.
Crew manager Gary Yorke said: "The driver was actually thrown from his vehicle on impact, and we were at the incident for about an hour and a half making the area safe."
The air ambulance also attended, but no-one else was injured.
Traffic was brought to a standstill as the M4 was closed in both directions for about an hour. The eastbound carriageway was still shut at 6pm, along with one lane of the westbound carriageway, and motorists are being warned to expect severe delays.