Four vehicles have been involved in a crash between Haydon Bridge and Bardon Mill.
One person has died in the collision, which was reported to Northumbria Police at 9.55am today.
Nine other people have been injured, and have been taken to hospital for treatment.
Northumbria Police Chief Inspector Dave Gould said: "The road remains closed in both directions and is expected to be until around 5pm this evening.
"This is to allow for collision investigation to be carried out and for it to be cleared and made safe."
Diversions have been put in place around the collision, police confirmed, but there may be delays.
According to the police, the diversions are as follows:
The diversions on the A69 are via the B6318 Military Road.
Westbound traffic is being diverted off the A69 at Greenhead onto the B630 to B6318.
Eastbound traffic is being diverted of the A69 at Acomb onto the A6079 to B6318.
Chief Inspector Gould added: "We have extra motor patrols officers out on the roads in the areas of the diversions to try and keep traffic moving as quickly and safely as possible. We will let you know as soon as possible when the road is re-open. Thank you for your patience and cooperation."
Anyone who witnessed the collision is asked to contact police on 101 quoting reference number 348 03/09/16.