The speed limit is set to be lowered on the A507 between Clophill and the Central Bedfordshire Council offices at Chicksands.
In a series of "improvements" to the route near Shefford, the 60mph speed limit is set to be reduced to 50mph, with 40mph introduced on the A507 Eagle Bends.
In a statement, Central Bedfordshire Council said the plans follow "numerous serious road incidents" in the Shefford area in recent years.
The statement notes that the council aims to "encourage motorists to go at appropriate speeds and prevent further incidents on this stretch of road".
Councillor Ian Dalgarno, executive member for community services, said: "These reduced speed limits and complementary safety measures and features should improve road safety along this stretch of the A507.
"It's an important road safety scheme and we ask road users to bear with us while we carry out the work.
"Road safety is a priority and we continue to urge motorists to take care of themselves and others, drive responsibly and appropriate to the prevailing conditions and adhere to the rules of the road at all times."
In addition to the lower speed limit, the work will incorporate new "slow" and "Think Bike" signs as well as upgraded road lining to promote safer driving.
Rumble strips on the road surface will "help motorists to maintain their position and drive on the correct side of the road".
New bollards on the verges to highlight the junctions and access points will also be introduced.
Work to make these changes began on Tuesday, September 20.
Night-time closures are in place from 8pm until 6am, and will be in place until Wednesday, September 28.
A signposted diversion will be in place during the closure periods. For eastbound traffic, traffic is asked to head north on the A6 to the A421 at Bedford, before heading southbound on the A600 towards Shefford - and vice-versa for westbound traffic.
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