England World Cup winner Stokes, playing on home turf, faltered with bat and ball at Chester-le-Street as South Africa claimed first blood in the Royal London Series.
Stokes' 105th and final ODI appearance was not one he will remember for his own contribution, bowling five stiff and wicketless overs for 44 runs before being dismissed for five, but the handful of ovations he received from a sell-out crowd was a touching reminder of the World Cup hero's enduring legacy.
England captain Jos Buttler told Sky Sports: "From myself and all England fans, we want to say thank you for everything he has done in this format of the game.
"Three years ago will live long in the memory, but every day he turns up for this team, whether it be training or a match - he puts in 100 per cent and he has been a fantastic ambassador for us in ODI cricket and we will miss him."
On the need for a response after another defeat, the new England ODI captain said: "I think we have been improving through the games we played.
"Of course we are missing some experienced guys and are going to lose another one (Stokes) as well, but that creates opportunities for others.
"It certainly feels a little like the changing of the times for us. We have to rebuild, but at the same time we have fantastic players with opportunities and other guys waiting in the wings to come back, so I am very confident in the team."
World Cup winning captain Eoin Morgan also paid tribute to Stokes.
"(England will miss) his all-round contribution, both in the changing room and on the field," Morgan said on Sky Sports.
"Probably more so in the changing room. He is a true leader and drags other people with him.
"He makes other players better by making them believing that anything is possible and it was a huge pleasure to be able to take the field with him.
"But at 31, having to retire from this format, it is incredibly sad. He will forever be remembered for 2019 throughout that tournament and in the final."
England bowler Mark Wood said: "He will go down as a legend in this format.
"He was the guy who won the World Cup in 2019, it is hard to forget that.
"He is a man who has put so much into it, and was part of the main leaders in the group that really stuck by everyone.
"It is sad for English fans. I am sad I am not going to get the chance to play with him in this format again, but we have got to move on."