The 42-year-old Blanco, who was capped 120 times by Mexico and played at three World Cups, said he will retire at the end of the Clausura championship with plans to go into politics.
Blanco began his career at America, who won a record 12th league title in the Apertura in December, in 1991 and helped them win the championship in 2005.
His chief concern he said, though, was to help Puebla avoid relegation. They are bottom of the relegation standings which are based on teams' average points over three seasons.
"I'm good and calm and will do my bit to have a good match which will be difficult. We're fighting against relegation so we need to get points wherever possible," Blanco told the sports daily La Aficion.
"We have a good team, the tournament has only just started but we can't let points slip away."
America's coach Gustavo Matosas said: "It will be very special Cuauhtemoc returning home with the crowd showing their appreciation for all he's done for Mexican football.
"I enjoyed watching him play, he's very creative and left his mark, but above he's a player with character.
"We're going to face one of the greatest (players) of America and Mexico. Players with quality and magic like Cuauhtemoc can always do something cheeky."
Puebla, who beat Tijuana but then lost at Veracruz, and America's arch-rivals Guadalajara, who are also fighting to avoid the drop, have picked up three points each from their opening two matches.
The Chivas, one place above Puebla in the relegation table, are away to Leones Negros in a Guadalajara city derby on Sunday.
(Writing by Rex Gowar; editing by Martyn herman)
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