Newey has held the position of chief technical officer since the team's second season in 2006, and leaves citing tiredness and the all-consuming nature of Formula 1 as reasons for his exit.
It is not yet confirmed where Newey will go after he leaves the reigning world champions. Ferrari are rumoured to be an option, though it is also possible the 65-year-old will take a break altogether.
Max Verstappen has benefitted greatly from Adrian Newey's designsRed Bull will start a new chapter without Adrian Newey in 2025
Horner insists on 'great relationship' with Newey
Newey's departure from Red Bull comes amid fractures in the team and controversy surrounding team principal Horner.
Adrian Newey has been linked with a move to Ferrari
"We have enjoyed a great relationship, and we continue to enjoy a great relationship.
"We are friends as well as work colleagues and he's done a huge amount for this team.
"We will be sad to see him leave but he's left the team in good shape and we've got a great team of people and strength and depth to take us forward," he added.