James Milner, Roberto Firmino, Naby Keita and Alex Oxlade-Chamberlain will all leave Liverpool at the end of the season, the club has confirmed.
All four players' contracts expire this summer.
They were all part of the side that won the Champions League in 2019 and Premier League in 2019-20.
BBC Sport understands Brighton are closing in on a deal for Milner, 37, who has won six major honours at Liverpool.
A statement from Liverpool said: "All four players will depart with our gratitude and appreciation for the contribution they have made."
The club added that special tributes would be paid to the players in the Reds' final Premier League home game of the season against Aston Villa on Saturday.
Liverpool boss Jurgen Klopp had already outlined the club's intentions to be active in the summer transfer window.
His side have had a difficult season but seven consecutive wins mean they now sit fifth in the Premier League and could still qualify for the Champions League.
Milner and Firmino joined the club in 2015 under Brendan Rodgers and went on to win a historic Premier League title in 2020 - the club's first top-flight triumph in 30 years - as well as the FA Cup last season.
Former Manchester City midfielder Milner, who has made 330 appearances for the club, has made 617 Premier League appearances, the third highest in the league's history.
Firmino became the highest-scoring Brazilian striker in Premier League history in 2019 and now has 80 goals in 254 top flight appearances but has not played since March.
The 31-year-old will be best remembered at Liverpool for his time playing alongside Mohamed Salah and Sadio Mane as part of a prolific front three under Klopp.
Klopp had said he wanted Firmino to stay and, although the forward had been in discussions over a new contract, he has chosen to move on.
Keita, who scored 11 goals in 129 appearances, signed in 2017 but has made just 12 appearances this season having struggled with injuries.
Meanwhile Oxlade-Chamberlain has also struggled for minutes this season, making just 13 appearances, the last of which was against Real Madrid in Liverpool's Champions League last-16 exit.
The 29-year-old joined in 2017 and has made 146 appearances for the club, scoring 18 goals.
Liverpool's summer of transition - analysis
Phil McNulty, BBC Sport
Liverpool's announcement that the experienced quartet of Firmino, Milner, Keita and Oxlade-Chamberlain are leaving Anfield came as no surprise.
What it does confirm, however, is that this will be a summer of transition as manager Klopp refreshes a squad that will end the season without silverware after chasing four trophies last term, winning the FA Cup and League Cup.
Firmino has been a central figure in Liverpool's outstanding trophy haul under Klopp but the succession plan for the Brazilian already appears to have been dealt with by the signing of Cody Gakpo.
It is in midfield where Klopp will focus attention as Milner, Keita and Oxlade-Chamberlain leave and with captain Jordan Henderson celebrating his 33rd birthday in June.
Jude Bellingham will not be coming but Liverpool will have plans in place for serious strengthening in that area, with Chelsea's Mason Mount and Brighton's Argentina World Cup winner Alexis Mac Allister very much on a list of potential summer targets.
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