The fourth-generation Lexus LS flagship sedan (chassis code XF40) premiered in January 2006 for the 2007 model year. Styled under L-finesse guidelines, it was the first LS offered in both standard and long-wheelbase (LS 460 L) configurations. Long-wheelbase models could be equipped with an Executive Class rear seat featuring a power Ottoman footrest and Shiatsu massage function. It introduced the world's first eight-speed automatic transmission and an Advanced Parking Guidance System.

The LS 460 housed a 4.6-liter 1UR-FSE V8 producing 380 horsepower. In 2007, Lexus launched the flagship LS 600h L hybrid, combining a 5.0-liter V8 engine with electric drive for 438 total system horsepower transmitted through full-time all-wheel drive. A major 2012 redesign restyled over 3,000 components, integrating the corporate spindle grille, full-LED headlights, and an F Sport performance package.