The dual carriageway was closed both ways between Riverside and Mereway.
Traffic was backed up from Queen Eleanor to Billing and beyond. National Highways said there were at least two miles of queues in both directions with a diversion in place following a single-car collision.
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Emergency services were on scene.
Northamptonshire Police tweeted earlier: “Motorists are urged to avoid the A45 at Barnes Meadow in Northampton following a serious road traffic collision this afternoon.
“The road is closed in both directions while emergency services attend the scene.”
A police spokeswoman added: “Officers from our Serious Collision Investigation Unit remain at the scene.
“Tailbacks have been cleared however the westbound will remain closed whilst investigations take place.”
UPDATE: National HIghways tweeted at just after 8pm: “The A45 is now open in both directions between the A43 and the A5076 near #Northampton following an earlier serious collision. Delays are clearing well in the area. Thanks for your patience and have a safe journey.”