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The Lexus LS (XF40) is the fourth generation of the Lexus LS line of full-size luxury sedans. Lexus debuted the model line at the 2006 North American International Auto Show, with variants including the standard wheelbase LS 460 (USF40) and long wheelbase LS 460 L (USF41); the chassis codes (USF40/USF41) are derived from the fourth generation XF40 platform code and UR series engine designation. In development from 2001, the final design was selected for the V8 models in late 2003, with the hybrid variant's design finalized in 2004. Introduced at the 2006 New York International Auto Show, all-wheel drive hybrid models, the standard wheelbase LS 600h (UVF45) and long wheelbase LS 600h L (UVF46), joined the lineup in the 2008 model year. The LS 460 and LS 460 L models feature a 4.6 L UR series V8 and an 8-speed automatic transmission, while hybrid models are powered by a 5.0 L UR series V8 engine equipped with electric motors, with a continuously variable transmission and all-wheel drive. All-wheel drive versions of the non-hybrid LS 460 (USF45) and LS 460 L (USF46) models were introduced at the 2008 Moscow International Automobile Salon. The XF40 received updates for the 2010 and 2013 model years.

Since its introduction, multiple fourth generation Lexus LS models have been sold worldwide, including standard, long wheelbase, hybrid, and all-wheel-drive versions. At its introduction, the LS 600h L became the most expensive sedan produced in Japan, with a sticker price of approximately US$125,000.

The fourth generation Lexus flagship was the first LS to receive the styling cues of Lexus' new design direction, L-finesse. The design features body forms running the length of the car, with wheel arches, arrow-shaped chrome trim, a grille set slightly below the level of the headlamps, and a fastback rear decklid. Compared to the previous generation LS, the forward and aft coefficient of lift was reduced to 0.02 and 0.01, respectively, while aerodynamic drag remained the same (C_d 0.26). Exterior-wise, the LS 460 L has a similar profile as the LS 460, with identical overhangs in both front and rear; the rear passenger doors are noticeably longer in the stretched model. Design patents for the vehicle's exterior design, including front and rear fascias, side windows, and lights, were filed with the United States Patent and Trademark Office on 3 October 2005.

Additional details of the design include adaptive headlamps housed in hand polished surrounds designed to look like Baccarat crystal tumblers, chrome exhaust vents integrated into the rear bumper, and "L"/"S" curve shapes. The fenders are produced using a 5200-ton press, which when introduced made it the world's strongest stamping press. The model's new paint finish is applied to bare-metal body panels which are first prepared by a six-axis buffing robot with 3D movements,^[9] the entire paint finish is wet-sanded twice by hand between layers of paint application. Both front and rear window frames are each constructed from a single die-cast zinc piece, plated in chrome and then polished by hand.

interior features include a 19-speaker Mark Levinson Reference Surround Sound System, Gracenote, and a 30 GB HDD with room for 2,000 songs. The fifth generation HDD-based Lexus navigation system features XM NavTraffic, a real-time traffic monitoring system with dynamic rerouting (in the U.S., and similar systems elsewhere). Keyless SmartAccess with push-button start, Optitron instrument panel with TFT multi-information display, auxiliary MP3 player input, and a 5-position tire pressure display are standard equipment. A 24-hour concierge/emergency aid service, Lexus Link (later Lexus Enform), was offered in North America, with the analogous G-Link system offered in Japan. Japanese market LS sedans also feature MiniDisc compatibility, television reception, onboard security surveillance cameras, and remote cellphone access.

Comfort and convenience features range from a 16-way adjustable heated and cooled driver seat to a rear cabin with power reclining memory seats, a cool box, and five powered sunshades. Certain versions of the LS can be equipped with climate control features such as first automobile ceiling air diffusers, air purifiers, air ionisers, and four-zone climate control with infrared body temperature sensors. The leather on the seats and steering wheel are made smoother than previous models, due to being buffed longer in production, the steering wheel is buffed for three hours and incorporates a whip stitching pattern. Upgraded materials (such as a headliner made out of ecsaine, a suede-like material used by couturier Yves Saint-Laurent) are offered for the interior. Inside the wood veneer trim has been laminated to aluminum instead of fiberglass by Yamaha's piano craftsmen. A special-order "Executive" seating package on long wheelbase models includes a rear seat DVD entertainment system with ceiling fold-down LCD screen, fixed center console with a swivel tray table, and a passenger-side shiatsu and shoulder massaging ottoman seat.

Lexus released an official photograph of its restyled XF40 series in July 2012 which will be released for the 2013 model year. The substantial update incorporates the new Lexus corporate fascia, comprising the "spindle" grill and consequently sees the fitment of a redesigned hood, reshaped front fenders and headlamps, plus a new bumper. These styling revisions see the retention of the side profile and doors, including rear fenders. Thus, the newly designed tail-lamps, trunk lid, and rear bumper are only partially modified. The sport package, still only offered on the standard wheelbase variant but now including all-wheel drive as well as rear-wheel drive, is now known as the F-Sport.

Reportedly, the refresh involved 1000 engineers and replaced 3000 out of 6000 new parts.