Martino played mostly for Newell's Old Boys in his native Rosario. He holds the record of appearances with the team playing a total of 505 matches in all official competitions.
Martino was assigned as head coach of the Paraguayan national football team in February 2007, replacing UruguayanAnibal Maño Ruiz. His knowledge and success while coaching Paraguayan clubs were the parameters that positioned him as the best option for the job (other candidates were Nery Pumpido and Miguel Ángel Russo). Previously, Martino had won the Paraguayan league 4 times from 2002 till 2006.
On 5 July 2010, Martino announced that he would be stepping down as Paraguay coach on their return from the 2010 FIFA World Cup. Martino confirmed that with his four-year contract expiring, he would not be extending his spell in charge of the national side. However, on 10 July 2010, Martino agreed to stay on as Paraguay coach until after the 2011 Copa America.