Valdano, who was ousted in May after losing a power battle with Real coach Jose Mourinho, said the gap between the wealthy pair and the rest was likely to get bigger.
"In the future Madrid and Barcelona will have to look to teams that are going at the same speed, and that will lead to a European league," he told Cadena Ser radio.
"Before I defended Real Madrid's interests but now I see things from a different perspective," the former Real and Argentina player added.
"The gap between the big two and the rest is getting ever larger. If you look to the future you have the feeling that it will only get worse.
"Two teams which have the rest of the world as their market and the others only their local community.
"There will come a time when that won't be convenient for the two big clubs either."
The difference in class and spending power between Spanish and European champions Barca and Real - the world's richest clubs by revenue - and their domestic rivals was underlined by their emphatic wins in their opening league games of the season.
TRANSITION PERIOD
Barca crushed Villarreal, who are competing in this season's Champions League, 5-0 at the Nou Camp on Monday, while Real demolished Real Zaragoza 6-0 away the previous day.
The results prompted the president of Villarreal to accuse Barca and Real of killing Spanish football, while the Sevilla president said La Liga was "a load of rubbish".
The dominance of Barca and Real derives in part from their control of revenue from television rights, which gives them a far bigger share of the pot than rivals in other major European leagues.
Spain has yet to adopt the system of collective bargaining and income sharing used in other competitions like the English Premier League.
Javier Faus, a vice president of Barca, told Reuters in February the club would like to see an expanded Champions League and floated the idea of reducing the number of clubs in top domestic divisions to free up time for more continental matches.
However, he said it was unlikely Barca or Real would ever quit domestic competition entirely.
"We are going through a period of transition, it depends what happens in Spain and other leagues," Valdano told Cadena Ser, which has hired him as a commentator.
"The problem is that the Premier League works, Germany works. There is a lot of passion for football. I don't see them being very enthusiastic about leaving their national leagues."
