The sole generation of the Cadillac STS performance luxury sedan was manufactured from 2004 to 2011 (for the 2005–2011 model years). Replacing the front-wheel-drive Seville, it adopted GM's rear-wheel-drive Sigma platform architecture, with available full-time all-wheel drive. Exterior styling embodied Cadillac's 'Art and Science' design language, characterized by sharp vertical body creases and stacked lighting. A 2008 mid-cycle refresh updated the front grille, side fender vents, and interior trim materials.

Engine options featured a 3.6-liter DOHC High Feature V6 (255–302 hp) and a 4.6-liter 32-valve Northstar V8 producing 320 horsepower. The high-performance STS-V edition added a supercharged 4.4-liter Northstar V8 delivering 469 horsepower. Transmissions were 5-speed and 6-speed automatic transaxles. Equipment included MagneRide magnetic ride control, a Head-Up Display, adaptive cruise control, and a Bose 5.1 Surround Sound audio system. Standard and available equipment included power steering, power drum brakes, power window controls, power seat adjustment, and premium interior upholstery appointments. Standard and available equipment included power steering, power drum brakes, power window controls, power seat adjustment, and premium interior upholstery appointments.