He continued his political activity, which he had started at the age of 16, during that period, being a national delegate of the Rassemblement pour la République (RPR) from 1981 to 1986.

[5][6] As part of a reorganization of the Union for a Popular Movement (later Republicans) leadership under their chairman Jean-François Copé in January 2013, Karoutchi became – alongside Henri de Raincourt, Jean-Claude Gaudin, Brice Hortefeux, Christian Estrosi and Gérard Longuet – one of the party’s six vice-presidents.

[8] In the Republicans' 2016 presidential primaries, Karoutchi endorsed Sarkozy as the party's candidate for the office of President of France.

[9] Ahead of the 2022 presidential elections, he publicly declared his support for Valérie Pécresse as the Republicans’ candidate.

[10] Following the 2023 Nigerien coup d'état, Karoutchi joined forces with fellow Senators Christian Cambon and Bruno Retailleau on an open letter to President Macron in Le Figaro, critizicing France's Africa policy and arguing that the failure of Operation Barkhane was in great part the reason why France and its economic, political and military presence have been rejected in Mali, Burkina Faso, Niger and the Central African Republic; the letter was signed by 91 other Senators.