Zanetti came on as a 52nd minute substitute during a 4-1 win over Lazio that booked Inter's place in the Europa League for next season, a final high for a player who was a rock of consistency in a topsy-turvy two decades at the club.
It was his 857th appearance for Inter since signing for the club in 1995, when he became Massimo Moratti's first purchase as Inter president, and he could make one more in their final Serie A match of the season at Chievo next week.
"From the moment he arrived at Inter he always honoured the shirt and always made us proud to be Inter fans," former Inter owner Moratti said on Saturday.
"We have won a lot with him, everything. But I think that a person like him deserves all that and also deserves all of our affection and to be remembered for ever."
The Argentine's 614 Serie A appearances is bettered only by former AC Milan and Italy defender Paolo Maldini but is by far and away the most of any foreign player to play in Italy.
In that time Zanetti has won five league titles, scored in a 3-0 1998 UEFA Cup final win against Lazio and played a key role in the treble-winning 2010 side that claimed the club's first European Cup in nearly half a century.
But he was also part of the team that handed the league title to arch-rivals Juventus in 2002 after a spectacular collapse in the final weeks of the season. A 4-2 defeat at Lazio saw them drop from being league leaders to third place in the space of 90 agonising minutes.
Zanetti will leave the game a symbol of better times for Italian football, when one-club legends like Maldini, Alessandro Del Piero and Francesco Totti helped make Serie A the toughest, and arguably the best league in the world.
Next season only Totti will be left, and his role at Roma is becoming increasingly marginal.
"It wasn't easy to take this decision, I've given everything I had," Zanetti said. "I'm glad to be able to quit when I'm physically and mentally fit."
Moratti's sold his controlling interest in the club to Indonesian Erick Thohir last year and is now at the club only in an honorary capacity.
Thohir, though, has assured fans that Zanetti will take up a backroom role but so far has refused to say what position.
Zanetti, who won 145 caps for his country, was already advising the next generation.
"I'll tell the lads who pull on the Inter jersey in future that they have to honour it and defend it as I've had the privilege of doing," the Argentine said.
"It's important to have that sense of belonging and understand what it means to play for Inter and defend these colours across the world. That's what they need to understand."
During his on-pitch speech, Zanetti called out fellow Argentine and Inter treble winners Walter Samuel, Esteban Cambiasso and Diego Milito to take the applause from the crowd.
Both Milito and Samuel are expected to leave before next season in further changes post Moratti.
"I'll miss lots of things: the dressing room, drinking Mate (a hot drink popular in South America) with Samuel and Milito and the training camps," Zanetti said.
"I'll carry it all with me for the rest of my life."
- Sports & Recreation
- Massimo Moratti