Suzuki said on Wednesday they had come to an agreement with championship promoters Dorna to leave MotoGP at the end of this season, four years before the end of their contract.
Their current deal with the sport started in 2015 and was due to finish in 2026.
In May, the Japanese manufacturer said they wanted to quit MotoGP for financial reasons, which were also cited by the team on Wednesday.
"Motorcycle racing has always been a challenging place for technological innovation, including sustainability, and human resource development," Suzuki's representative director and president Toshihiro Suzuki said in a team statement.
"This decision means that we will take on the challenge to build the new motorcycle business operation by redirecting the technological capabilities and human resources we have cultivated through the motorcycle racing activities to investigate other routes for a sustainable society," he added.
Suzuki left MotoGP at the end of 2011, before returning in 2015.
Since they returned seven years ago, they have won the riders' title in 2020 when Joan Mir topped the standings with teammate Alex Rins third.
In the 500cc era, Barry Sheene, Marco Lucchinelli, Franco Uncini, Kevin Schwantz and Kenny Roberts Jr. won world titles riding Suzukis.
This season, Mir is seventh and fellow Spaniard Rins in eighth in the overall standings after 11 of the campaign's 20 races.
According to reports the pair are likely to sign contracts with Honda for next year.
In MotoGP's current format, there are 24 bikes on the starting grid in each race, although wildcard entries increased that to 25 on occasions this season.
Ducati have eight bikes on the grid, while Suzuki and Aprilia are the only manufacturers with just two bikes on the starting grid.
The 24-bike format is fixed until 2026, when the current contract between the International Motorcycling Federation, Dorna and the International Racing Team Association, which represents the six manufacturers, ends.