He was the chairman of the centre-left Spanish Socialist Workers' Party (PSOE), and from 23 April 2009 until 7 September 2013 he held the position of President of the Regional Government of Andalusia.

He joined the PSOE at the beginning of the 1980s, and after the socialist victory in the Andalusian parliamentary elections of 23 May 1982 (the first such elections to be held, since the Spanish transition to democracy), served as vice minister of Labour in the Andalusian governments presided over by Rafael Escuredo and José Rodríguez de la Borbolla, until in 1986 when he was named vice minister of Health.

In April 2004, Manuel Chaves named him minister of economy and finance, and later, in 2008, he was given the additional role of second vice president of Andalusia .

Griñán had to make an agreement with United Left to secure a majority coalition government and keep his position as the President of Andalusia.

On 15 June 2015 he left his seat as senator autonomy after being charged in the corruption scandal case named ERE.

Griñán is a recipient of the Grand Cross of the Order of Charles III, which gives him the honorific of Excelentísimo Señor.