The HS was released in July 2009 as the first dedicated hybrid line bearing the Lexus brand. While sharing some of the components used in the Prius, including the THS II hybrid system with reduction gears, an electric motor with an output of 143 PS and 270 Nm (27.5 kgm), and batteries, the Lexus HS was fitted with a 2.4-liter 150 PS engine (2AZ-FXE) instead of the 1.8-liter unit, developing a total output of 190 PS to drive its front wheels. The suspension system combined MacPherson strut for the front and double wishbone for the rear. As with the LS 600h and RX 450h series, LED headlamps were adopted for all model variations. To reduce the burden on the environment, eco-friendly plastics were adopted for some interior components. With the body dimensions of 4,700 mm in length, 1,785 mm in width, and 1,505 mm in height, with a wheelbase of 2,700 mm, the Lexus HS offered fuel efficiency of 23.0 km/l (10-15 mode) and 19.8 km/l (JC08 mode).

The Lexus HS has a Toyota-brand sister model marketed under the name Sai.