They say the victim was taken to University Hospital Coventry following a collision involving a white grocery delivery van in Barrack Road at 4.20pm on Thursday (November 24).
It is the third serious crash involving pedestrians on a half-mile stretch of the A508 in less than six months.
Officers are appealing for witnesses after last night's collision, close to Northampton International Academy.
Barrack Road was closed both ways for up to six hours between St George's Avenue and Regent Square for crash investigation work.
Officers from the Serious Collision Investigation Unit are appealing to anyone who may have been in the area at the time and could have information, particularly those that may have dashcam footage, to get in touch by calling the Drivewatch Hotline on 0800 174615 using incident number 377 of 24/11/21.
Mum-of-four Dulce Lina Mendes Pereira, aged 39, and her unborn child both died after a collision involving a Nissan Pathfinder at the junction of Greyfriars and Horsemarket on the A508 on May 29.
James Craigie, 30, from Stoke Bruerne, was charged with causing death by dangerous driving and child destruction days after the crash. But a court appearance set for July was delayed and a spokesman for Northamptonshire Police says no new date has yet been set.
Earlier this month, 56-year-old Karl Peter Chambers also died after a collision with a black Ford KA while crossing Broad Street to get to his home in Spring Boroughs.
Police confirmed a Kettering man quizzed following the crash remains still under investigation.
Following the death of Mr Chambers, West Northamptonshire Council confirmed it is looking at what safety improvements can be made on the stretch of road.
A spokeswoman said: "The locations of the incidents to are part of a Red Route which was last reviewed in late 2018 as part of a larger study.
"These are reviewed regularly based on accident statistics to allow prioritisation of any safety and improvement schemes that might be required.
"A further review is currently programmed to take place in January 2022."