The palace was built for Marie de Médicis, mother of king Louis XIII of France and of Gaston, duc d'Orléans, just near the site of an old hôtel particulier owned by François-Henri de Montmorency, duc de Piney-Luxembourg, hence its name (now called Petit Luxembourg, home of the president of French Senate). Marie de Médicis desired to make a building similar to her native Florence's Palazzo Pitti, and to this effect had the main architect Salomon de Brosse send architect Clément Metézeau to Florence to obtain drawings. Marie de Médicis bought the structure and its fairly extensive domain in 1612 and commissioned the new building, which she referred to as her Palais Médicis, in 1615. Its construction and furnishing formed her major artistic project, though nothing remains today of the interiors as they were created for her, save some architectural fragments reassembled in the Salle du Livre d'Or.The suites of paintings she commissioned, in the subjects of which she expressed her requirements through her agents and advisors, are scattered among museums.
A series of twenty-four triumphant canvases were commissioned from Peter Paul Rubens. A series of paintings executed for her Cabinet doré ("gilded study") was identified by Anthony Blunt in 1967. To the right of the block of the Luxembourg, erected at the same time, was the mass of the Palais du Petit-Luxembourg (see below).