A new section will run from the Black Cat roundabout to the Caxton Gibbet.
The first spades are in the ground in Roxton, near St Neots, after a special groundbreaking ceremony with South Cambridgeshire MP Anthony Browne.
The full plans include a new 10-mile dual carriageway linking the A1 and A421 Black Cat roundabout to the A428 Caxton Gibbet roundabout.
Both existing roundabouts will be upgraded into modern, free-flowing junctions with a new junction added at Cambridge Road, in a bid to improve access to St Neots and its train station.
Nicola Bell, National Highways Executive Director:
"This project highlights National Highways’ commitment to delivering major projects that make lasting impacts for people, communities, and businesses.
"The start of construction represents a culmination of meticulous planning, collaborative efforts, and a steadfast commitment to enhancing the nation’s infrastructure.
"We are proud to be part of a project that will lay the foundations for a more resilient and connected future."
National Highways say the upgrades will transform the region, enhance connectivity, alleviate congestion, and improve road safety.
It's hoped the scheme will improve journeys between Milton Keynes, Bedford and Cambridge, with drivers saving up to an hour-and-a-half on their journeys every week.
The road is expected to open to traffic in 2027.