The sixth-generation Lexus ES sedan (chassis code XV60) debuted at the New York International Auto Show in April 2012. Transitioning to the larger Toyota Avalon platform, the wheelbase grew by 1.8 inches, delivering class-leading rear legroom. Exterior highlights included Lexus's signature spindle grille, L-shaped LED daytime running lights, and dual exhaust ports. Cabin technology introduced the Remote Touch interface, an 8-inch display screen, and the Lexus Safety System+ driver assistance package.

Powertrain choices featured a 3.5-liter 2GR-FE V6 producing 268 horsepower on the ES 350, a 2.5-liter four-cylinder engine on the ES 250, and the first hybrid model, the ES 300h, combining a 2.5-liter Atkinson-cycle engine with an electric motor for 200 total system horsepower. A 2015 facelift brought a bold front spindle grille, LED headlights, revised steering wheel design, and sound-insulating acoustic glass.