He started his political career as member of the Radical Civic Union party (UCR), becoming Governor of the Province of Mendoza in 2003.
He was expelled from the UCR in 2007, and was then selected by presidential candidate Cristina Fernández de Kirchner, of the ruling Front for Victory (FpV), as her candidate for vice-president in the elections of that year, which they won.
His popular prestige got a big boost in 2008, when the Senate was voting on a controversial and contentious law to increase taxes on grain exports.
The voting ended in a tie, which gave Cobos, as President of the Senate, the deciding vote.
In a stunning and now notorious move, he voted against the law.
This led to strong criticism from his party, who deemed him a traitor, and approval from sectors of the population that opposed the government.
As he further distanced himself from the FPV, the UCR revoked his expulsion from the party.
By 2010, he was considered a potential candidate for the 2011 presidential elections.