He was replaced in the 84th minute and tearfully embraced all his team-mates, boss Xavi and the entire Barca bench.
The 35-year-old will retire after Tuesday's trip to Osasuna, although it is not certain he will play in that.
After the game he gave a speech on the pitch, saying: "I was born here and I will die here."
He added, "When you get older, you realise that sometimes to love is to let go. I'm convinced that I'll be here again in the future.
"I love Barca. That's why I consider it's the right moment to go. This is not a goodbye."
There were several tributes to him on his farewell night at the Nou Camp.
Pique, who was named captain, walked on to the pitch with his two sons, as all his team-mates wore shirts with his name and number three on the back.
The ex-Spain defender announced his decision on Thursday, despite having 18 months left on his deal, and his exit will help Barca with their wage bill.
Pique won 30 trophies and made 616 appearances for Barca after joining in 2008 from Manchester United.
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