RAF Lakenheath will host the largest aerial exercise of its type with more than double the number of aircraft engaging than ever before.
For the first time, the drill, called Point Blank, will include the French air force alongside aircraft and staff from the RAF and the US Air Force (USAF).
More than 40 aircraft will take part in the exercise, due to take place on Tuesday, with around 200 to 250 military staff involved for roughly an hour.
The exercise will see pilots tasked with simulated surface to air missile threats and air to air attacks to simulate combat situations in 'non-permissive environments', where government forces do not have control of the territory an operation is due to take place in.
Two F-35s, both from RAF Marham, 16 F-15s from Lakenheath, four British Typhoons and four French Rafale will be the main jets in the exercise.
Major general John Wood from the USAF said: 'It is important we do this exercise because we are friends, and friends and allies when we work together we are better and that is the opportunity we have in front of us.
'We are already at a high state of readiness but readiness can only be maintained if you exercise and train for it every day and think about it.'
Air commodore Jez Atteridge from the RAF said: 'As we saw over the last weekend we still have a challenge with Russia challenging the international rules-based order so therefore we need an insurance policy.
'Point Blank gives us the opportunity to stay ready, and if we stay ready we don't have to get ready.'
He added: 'East Anglia is the epicentre of combat air so it is and it will remain absolutely important for us both for our relationship with the USAF in Europe and also with the local communities here who actually provide us with all the life support we need to maintain that great air force capability that we are allowed to deploy today.'
Colonel Jason Camiletti, one of the US pilots flying the mission, said: 'We will be making that environment as realistic as possible. 'Quite frankly, we are going to go in there, we are going to kick the door down, accomplish the objective we need to and we are going to get back.'
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