After starting out at Newell's Old Boys in 2000, he went on to spend his professional career with Zaragoza and River Plate, appearing in 246 competitive matches with the former club and winning the 2004 Copa del Rey, adding several more accolades during his two spells with the latter and going on to be one of the most decorated players in their history.

[3] Born in Las Rosas, Santa Fe, Ponzio started his career in the youth system of Newell's Old Boys in neighbouring Rosario, going on to make more than 100 official appearances for the club.

However, when Zaragoza finished sixth in the 2006–07 campaign and qualified to the UEFA Cup, Ponzio had already left, moving in January 2007 to Club Atlético River Plate.

He scored his first goal for his new team in the 2007 edition of the Copa Libertadores, against Chile's Colo-Colo.[6] In January 2009, Ponzio returned to Zaragoza signing a four-and-a-half-year contract, with the club now in the Segunda División.

[11][12] On 4 January 2012, aged 30, Ponzio, whose link in Aragon ran until June, left struggling – in sporting and financial terms – Zaragoza and returned to River Plate for personal reasons, agreeing to a three-and-a-half-year deal.