He served as President of the Languedoc-Roussillon Region from 2004 until his death: prior to that, he had been mayor of Montpellier for 27 years, and was also a former member (député) of the National Assembly.

Building on the trend started by his predecessor François Delmas, who landed the Southern Europe IBM factory and headquarters as well as the scientific university, Frêche expanded Montpellier in all directions, propelling it from the 25th-largest city in France to the eighth, in less than 30 years.

This could have been due to both the fact that Frêche was an embarrassing figure for the socialists, prone to multiple politically incorrect speeches with racist overtones, and his alleged refusal to let the Socialist Party be secretly financed by fake bills issued by the private company Urba (Urba would cause a political scandal in France).

He had antagonized François Mitterrand as early as the foundation of the current French Socialist Party in 1971, being cast aside even at that date.

Frêche continued to attract controversy after his expulsion from the Socialist Party, insulting former Socialist Prime Minister Laurent Fabius in the run-up to the 2010 regional elections, saying "I've got a problem voting for that guy from Haute-Normandie, he doesn't look too Catholic" (Fabius has Ashkenazi Jewish roots).