At around 8.40am this morning (7/3) a black Nissan vehicle in lane four westbound was in collision with a white van just before junction 12.
Sadly, as a result of the collision, a woman, aged in her sixties, died at the scene.
Two other people suffered serious injuries and were taken to hospital, where they both remain in a serious condition.
The carriageway was closed in both directions while emergency services dealt with the collision.
Lanes one to three eastbound have now re-opened, but the westbound carriageway remains completely closed and is likely to remain so for much of the day.
Investigating officer Detective Constable Mark Dunne of the Serious Collision Investigation Unit, based at Three Mile Cross, said: “Tragically, as a result of a serious collision this morning, a woman has died and two others have been seriously injured.
“The woman’s next of kin have been made aware and are being offered support by specially trained officers, and my thoughts and the thoughts of Thames Valley Police remain with them at this extremely difficult time.
“I am appealing to anybody who was driving on the M4 this morning at around the time of the collision to please contact 101, quoting incident reference 320 (7/3) if you witnessed what happened.
“I would also like to hear from anybody who may have dash-cam footage to please check this, and if it has captured the collision, or the moments leading up to the collision, to please get in touch with us.”