The motorway has been closed between junctions 5 for Shadsworth and 4 for Blackburn South after a fault was spotted at around 10.30am on Tuesday.
A diversion has been put in place but drivers are being asked to avoid the incident.
The road will now not be reopened until the early hours of the morning said Highways England as work continues to fix a bridge expansion joint.
A spokesman for Highways England said: "The M65 westbound carriageway between J5 and J4 is fully closed due to a carriageway defect.
"Our specialist crews are en route to assess and fix. Long delays now building on the approach from J7.
"Part of the bridge joint is exposed and there is a concern for safety regarding debris coming from it."
Highways England has said that the closure is likely to remain in place throughout the evening rush hour.
Drivers are asked to check before they travel and to plan alternative routes if possible.