Highways closed the A45 eastbound between the A428 Barnes Meadow junction to the A509 Wilby Way junction after the crash, which happened at around 6.15am.
The closure has caused miles of tailbacks for anyone travelling in that direction throughout the morning.
Police have since confirmed that a van went into the back of a flatbed lorry.
The Warwickshire and Air Ambulance landed nearby as all emergency rushed to the scene.
The van driver is said to have non-life threatening injuries. No one else was hurt.
Highways England tweeted just after 11.15am: "The A45 has reopened following a serious collision this morning. there will be traffic queues around Barnes Meadow/Riverside area but these will clear over the next 20 minutes or so."
Highways team explain why such a long stretch of A45 in Northamptonshire is closed