Australian Ewan, 30, who started his World Tour career back in 2014 for the now Jayco-Alula team, also rode for Belgian team Lotto-Soudal before joining INEOS at the start of 2025 after a turbulent two years inside the professional peloton.
In a statement, Ewan said 2023 and 2024 were the reasons for his immediate retirement.
He said: "The truth is that even when I crossed the line first, that feeling - the one you chase for years - faded quicker than it used to.
"My experiences of the past two seasons, in particular the second half of 2024, has taken a significant toll on my relationship with the sport. I'm happy I didn’t let that period define the end of my career and I am proud of what I achieved in a short but successful time with the INEOS Grenadiers."
In a career that Ewan described as "exceeding every expectation I had", the Australian sprinter won five stages at the Tour de France between 2019 and 2020 as well as five stages at the Giro D'Italia and one at La Vuelta a Espana.
Away from the grand tours, Ewan was prolific at his home race, the Tour Down Under, winning nine stages.
His unique sprinting style of leaning over the handlebars to create an incredibly aerodynamic position was striking, and was on show just a month ago, when he picked up his final victory of his career, taking stage two at Itzulia Tour.
INEOS Grenadiers CEO John Allert lauded Ewan for his racing style, saying: "Thank you Caleb, on behalf of INEOS Grenadiers and everyone in our beautiful sport, for thrilling us with your unique and explosive brand of racing.
"You leave the sport with our respect and best wishes, and as a winner - in every sense of the word."
More to follow.