Honda will leave Formula One to focus on zero-emission technology at the end of the 2021 season, leaving Red Bull and Alpha Tauri needing to find a new engine partner from that point onward.
The decision was made at the end of September and the company does not intend to return to F1, Honda chief executive Takahiro Hachigo said during an online news conference.
"This is not a result of the coronavirus pandemic but because of our longer-term carbon-free goal," he said.
Honda returned to F1 in 2015 in partnership with McLaren before switching to Toro Rosso in 2018 and joining forces with Red Bull in 2019. It will now accelerate development of zero-emission technologies such as fuel cells and batteries.
"We understand how difficult it has been for Honda Motor Company to reach the decision. We understand and respect the reasoning behind this," Red Bull team principal Christian Horner said in a statement.
Both Red Bull and Alpha Tauri (the renamed Toro Rosso team) have won grand prix this season, making Honda the only engine supplier to have won with two different teams in the V6 turbo hybrid era that started in 2014 and has been dominated by Mercedes.
"The shifting focus within the automotive industry has led to Honda's decision to re-deploy their resources and we understand and respect the reasoning behind this," Horner added.
"Their decision presents obvious challenges for us as a Team but we have been here before and with our strength in depth we are well prepared and equipped to respond effectively, as we have proven in the past."
Honda's departure will leave only Mercedes, Ferrari and Renault as Formula One engine-makers.
Horner said Red Bull, whose main driver is highly rated Max Verstappen, would evaluate their options as a group.
Red Bull won four constructors' titles in a row with Renault from 2010 to 2013, but the relationship with the French manufacturer soured in the V6 era, with the team branding the engines as Tag Heuer for a period.
Both Red Bull-owned teams have used Ferrari units previously, but the Italian manufacturer's power unit has lost performance this season.
Mercedes already supply Racing Point and Williams as well as their own factory team and are due to provide engines to McLaren, currently with Renault, next year.
"Whilst we are disappointed not to continue our partnership with Honda, we are enormously proud of our joint success, delivering five wins and 15 podiums for both Red Bull owned teams," Horner said.
He said Red Bull remained committed to the sport in the long term, having recently signed a new commercial agreement for the next five years.
"Our joint focus for the remainder of the 2020 and 2021 seasons are unchanged, to fight for victories and challenge for the championship," Horner said. "As a signatory to Formula One's latest Concorde Agreement, Red Bull Racing remains committed to the sport in the long term and we look forward to embarking on a new era of innovation, development and success.
"As a group, we will now take the time afforded to us to further evaluate and find the most competitive power unit solution for 2022 and beyond."