Horner has been at the helm since the brand joined the grid in 2005, leading them to eight Drivers' Championships and six Constructors' Championships in 20 years.
However, the team have endured a poor 2025 season and currently sit fourth in the team standings, largely due to the performances of Max Verstappen, with first Liam Lawson and then Yuki Tsunoda failing to get anywhere near the front of the field in the second Red Bull.
As a result, he's been relieved of his duties and will leave the team with immediate effect.
He looked set to depart last year following accusations of harassment from a former employee of the team, but ultimately remained in his role.
Reports at the time stated that numerous key figures - including Verstappen's father, Jos - wanted Horner to leave, and that the Brit was supported by key shareholder Chalerm Yoovidhya.
A year on, he's lost that support.
"We would like to thank Christian Horner for his exceptional work over the last 20 years," a team statement read.
"With his tireless commitment, experience, expertise and innovative thinking, he has been instrumental in establishing Red Bull Racing as one of the most successful and attractive teams in Formula 1.
"Thank you for everything, Christian, and you will forever remain an important part of our team history," said CEO Oliver Mintzlaff.
He'll be replaced by Laurent Mekies, the current boss of sister team Racing Bulls, whose role there will be filled by Alan Permane.
"It has been an amazing adventure to contribute to the birth of Racing Bulls together with all our talented people," said Mekies of his departure.
"The spirit of the whole team is incredible, and I strongly believe that this is just the beginning.
"Alan is the perfect man to take over now and continue our path. He knows the team inside out and has always been an important pillar of our early successes."