This event, the chief event of Lucien's life, was fatal to the cause of democracy of which he had been the most eager exponent. In one of his earlier letters to his brother Joseph, Lucien stated that he had detected in Napoleon “an ambition not altogether egotistic but which surpassed his love for the general weal; . . . in case of a counterrevolution he would try to ride the crest of events.” This suspicion became a dominant feeling, and the relations between Lucien and Napoleon became strained during the Consulate (1799–1804). Lucien believed that Napoleon's growing ambition for power was jeopardizing the cause of democracy. He accepted office as minister of the interior but was soon deprived of it because of political and personal differences with the first consul. Napoleon next appointed him ambassador to the court of Madrid (1800), where he again fell into disfavour. He returned to Paris and again opposed Napoleon's schemes. The breach was completed when Lucien was secretly married to Mme Jouberthou (Alexandrine de Bleschamps) despite Napoleon's express prohibition. Lucien's first wife, Christine Boyer, had died in 1800, and Napoleon had wanted him to marry the Spanish infanta Maria Luisa, the widow of Louis, king of Etruria. Ordered to leave France, Lucien lived in Italy.

In December 1807 Napoleon sought to come to an arrangement by which Lucien would be made a French prince, provided that he would agree to have his marriage annulled. Lucien refused and left for the U.S. He was captured at sea by the British and taken to England, where he lived under light surveillance until his return to Rome in 1814. He offered Napoleon his help during the Hundred Days (1815), stood by his side in Paris, and was the last to defend Napoleon's prerogatives at the time of his second abdication. The rest of Lucien's life was spent in Italy. His publications include an epic, Charlemagne ou L'Église délivrée (1814; “Charlemagne; or, The Church Delivered”); La Vérité sur les Cent-Jours (1835; “The Truth About the Hundred Days”); and Mémoires, of which only the first volume appeared (1836).