The crash happened between junctions 12 and 13 on the M4's westbound carriageway just after 11am this morning, Thames Valley Police said.
A 25-year-old man was airlifted to Southampton General Hospital in Hampshire with serious injuries and another person was admitted to the Royal Berkshire Hospital with minor injuries.
Ten others received minor injuries and were treated at the scene of the crash, which completely closed the westbound M4 for a time.
The eastbound carriageway was also closed for the air ambulance to land but it has now reopened, along with the westbound section.
More top news
Thursday night's forecast for the west of the region
Thursday night's forecast for the east of the region
Thursday afternoon's weather for the west of the region