The Luton-Dunstable busway will be closed for five days from Monday, August 17, till Friday, August 21.
The busway will be closed in both directions between Church Street Bridge and Skimpot Road.
It is closed to allow for essential maintenance works to be carried out.
Services will be diverted to an on-road route.
The busway connects Luton with Houghton Regis and Dunstable.
Arriva, Centrebus and Grant Palmer buses use the guided route that was officially opened in September 2013.
The busway was partially closed on Sunday, August 2, and Monday, August 3, following a collision which left the driver and two passengers badly injured.
The impact of the collision threw the driver of the bus through his cab window leaving the vehicle out of control and on the wrong side of the track.
One of the bus passengers jumped out of the moving vehicle and flagged down an oncoming bus to avoid what could have been a devastating collision.