Isère is one of the original 83 departments created during the French Revolution on 4 March 1790. It was established from the main part of the former province of Dauphiné. Its area was reduced twice, in 1852 and again in 1967, on both occasions losing territory to the department of Rhône.

In 1852 in response to rapid urban development around the edge of Lyon, the communes of Bron, Vaulx-en-Velin, Vénissieux and Villeurbanne were transferred to Rhône. In 1967 the redrawing of local government borders led to the creation of the Urban Community of Lyon (more recently known simply as Greater Lyon or Grand Lyon). At that time intercommunal groupings of this nature were not permitted to straddle departmental frontiers, and accordingly 23 more Isère communes (along with six communes from Ain) found themselves transferred to Rhône. The affected Isère communes were Chaponnay, Chassieu, Communay, Corbas, Décines-Charpieu, Feyzin, Genas, Jonage, Jons, Marennes, Meyzieu, Mions, Pusignan, Saint-Bonnet-de-Mure, Saint-Laurent-de-Mure, Saint-Pierre-de-Chandieu, Saint-Priest, Saint-Symphorien-d'Ozon, Sérézin-du-Rhône, Simandres, Solaize, Ternay and Toussieu.

Most recently, on 1 April 1971, Colombier-Saugnieu was transferred to Rhône. Banners appeared in the commune's three little villages at the time proclaiming Dauphinois toujours ("Always Dauphinois").

Isère was also the name of the French ship which delivered the 214 boxes containing the components of the Statue of Liberty.

Isère features many ski resorts, including the Alpe d'Huez, Les Deux Alpes, the 1968 Winter Olympics resorts of Chamrousse, Villard de Lans, Autrans. Other popular resorts include Les 7 Laux, Méaudre, Saint-Pierre-de-Chartreuse, Alpe du Grand Serre and Gresse-en-Vercors. At the department level, Isère is the third-largest ski and winter destination in France, after Savoie and Haute-Savoie. It also hosts Coupe Icare, an annual festival of free flight, such as paragliding and hang-gliding, held at the world-renowned paragliding site at Lumbin.

Grenoble has a dozen museums, including its most famous, established in 1798, the Museum of Grenoble. The European Synchrotron Radiation Facility (ESRF), an international research facility in Grenoble, is also open to visitors.

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