The third generation GS was first introduced as a 2006 model at the 2005 North American International Auto Show. The initial model lineup included the GS 300 (GRS190), with a 3.0 L V6 3GR-FSE engine, and the GS 430 (UZS190), with the same 4.3 L V8 used in the previous model. The GS 300 featured a direct-injection engine for all markets except for Continental Asia, excluding Singapore. The 3.0 L engine was also found in the Toyota Mark X as well as the Zero Toyota Crown. An all-wheel drive option was made available in the GS 300, thus becoming the first Lexus sedan to offer an all-wheel drive configuration. Production of the third generation began on January 24, 2005. The equivalent Aristo was not released as Toyota sought to align all world markets, including Japan, using Lexus as their luxury brand worldwide.

The third generation GS is the introductory Lexus model for the marque's new L-finesse design philosophy. Characterized by swooping lines, a fastback profile, and more muscular styling, the GS indicates the future direction of the Lexus lineup. The slingshot cabin on the GS was first previewed on the earlier Lexus LF-S concept.

The GS sedans also were the first to feature the latest generation of Lexus' SmartAccess keyless system–-adding a push-button start for the first time. Other unique features include a driver-side hidden panel for infrequently used controls, a standard touchscreen display in the center console, LED lighting in the cabin, and Bluetooth technology. A Mark Levinson premium sound system is optional. Unique to the Lexus GS series, each vehicle features an electrochromic instrument cluster which adjusts for the amount of reflected sunlight.

The GS 350 (GRS191), using the 3.5 L 2GR-FSE engine, replaced the GS 300 for the 2007 model year. Due to a change in SAE testing procedures, the 2007 GS 430 horsepower rating was changed to 290 (with 319 ft·lbf. of torque), while the V6-powered GS 350 was rated at 303 hp (with 274 ft·lbf. of torque). Lexus reports 0-60 times of 5.7 seconds for both vehicles.[3] A 4.6 L GS 460 (URS191) replaced the GS 430 for the 2008 model year. Equipped with a new 4.6 L 1UR-FE engine generating 342 hp (with 339 ft·lbf. of torque), the GS 460 also added an 8-speed automatic transmission. Lexus reports a 0-60 time of 5.4 seconds for the GS 460.[4]

Coinciding with the introduction of the GS 460, the GS lineup received an exterior refresh, including a revised forward bumper and headlights, turn signals added to the side mirrors, and new wheel options and exterior colors. Inside the vehicle, the GS received a redesigned steering wheel, revised instrument cluster gauges, and different trim pieces. Along with the hybrid GS 450h and previous GS 430 models, the V8-powered GS 460 offers the Active Stablizer Suspension System for improved handling.

In 2007, Consumer Reports dropped Lexus from 1st to 5th in their predicted reliability survey. The magazine blamed the 2006 first-year GS, which had problems in integrity, body hardware and sound system, as the sole reason for the slip. [1] Despite the reliability issues among 2006 GS models, the vehicle earned an "Recommend" rating from Consumer Reports for vehicle features and overall value.

In the U.S., the GS 350 begins at $44,150, while the GS 430 retails at $52,375.