The first-generation LaCrosse replaced the Century and Regal in North America beginning for model year 2005 as a five- or six-passenger, four-door, front-wheel-drive, V6-powered sedan using GM's mid-size W platform—and marketed in Canada as the Buick Allure.

The third generation was introduced for North America and China for model year 2017 using the GM Epsilon platform shared with the Chevrolet Impala, notably offering a mild hybrid powertrain combining 20-kilowatt (27 hp) electric and 2.5-liter Ecotec gasoline engine.

Using the MS2000 variant of GM's long-lived front-drive W-body platform, the LaCrosse was initially available with two powerplants and three trim levels: a 3.8 L 3800 Series III V6 available in CX and mid-level CXL, and a 3.6 L HFV6 V6 in the CXS model.

All LaCrosse models featured an acoustic package, marketed by Buick as QuietTuning, to reduce, block, and absorb cabin noise.

Features of the system included acoustical windshield and front side laminated glass; steel laminate on the front-of-dash body area; expanded baffles in the roof pillars; melt-on sound deadeners throughout the entire lower body structure; and sound-absorbing material throughout the engine, passenger, and cargo compartments.

Buick offered the LaCrosse as a five-passenger sedan, using front bucket seats and a console-mounted shifter, the console integrating with the upper instrument panel.

Regarding its styling, noted automotive journalist Warren Brown described the Lacrosse as a "delightful rendition of the automobile as functional art.

[17] All trim levels received a chrome exterior appearance package, factory remote start feature, XM Satellite Radio, telescoping steering wheel column, redundant steering wheel and climate control as added standard equipment (audio only post-MY 2006).

CX included a leather-wrapped steering wheel, theft-deterrent system, illuminated vanity mirrors, driver information center personalization, and hydraulic struts supporting both the engine hood and trunk lid.

To coincide its introduction with the first generation's MY 2008 facelift, Buick previewed the LaCrosse Super in March, 2006 in New York and again at the Buick Open in Grand Blanc, Michigan, in July 2006,[20] presenting it formally at the 2007 New York International Auto Show[21]—as a higher-content, higher-performance, and more exclusive LaCrosse sub-model.

Resurrecting the Super nameplate from Buick's 1930s–1950s model, the model featured minor interior and exterior tweaks as well as a 5.3-liter, 300-hp V8 engine shared with the Pontiac Grand Prix GXP and Chevrolet Impala SS, and Monte Carlo SS—engineered under the direction of former Corvette engineer John Heinricy with the GM Performance Division.

[22] Noting that the Super would share parts with Chevrolet and Pontiac variants, Heinricy said the LaCrosse aimed to balance performance and refinement for a smoother, quieter and more grown-up demeanor.

The Super used the heavier duty 4T65-E HD four-speed automatic transmission, magnetically sensitive variable-effort power steering (marketed as Magnasteer), and a steering rack with closer-fitting gear teeth, tighter bushings, and a stiffer torsion rod controlling the variable-effort power assist.

[23] Chassis tuning featured Bilstein mono-tube struts; larger rotors at all four disc brakes; full-range, powertrain- and brake-modulated traction control; revised suspension tuning with standard electronic stability control, marketed as Stabilitrak; dual exhaust with two 3.5-inch chrome tips; and 18-inch cast aluminum wheels with P235/50R18 all-season tires.

Interior features included a blue-faced instrument cluster with Super badging, dark faux chestnut wood trim, enhanced front seatback bolstering, split fold-down rear seats, redundant steering wheel–mounted radio and cruise controls, leather seating surfaces with inserts embossed to mimic woven leather (marketed as Dream Weave), heated front seats, remote start, premium sound system with nine speakers (marketed as Concert III), OnStar, and optional Bluetooth wireless technology.

[28] The IIHS also found that the 2006–08 model year LaCrosse had the second-highest fatality rate in the large four-door car class; only the Buick Lucerne fared worse.

[36][37] The exterior used faux vents and a falling swage line, marketed respectively as VentiPorts and Sweepspears—and making reference to styling elements Buick had incorporated in various forms since introducing them in 1949.

The second-generation used a long-wheelbase (LWB) variant of the Epsilon II platform, shared with the Opel Insignia, 2010–2012 Saab 9-5, and the Cadillac XTS.

The system consists of a 115-volt lithium-ion battery pack, a 15 kW electric motor capable of adding 15 horsepower of assist while accelerating, and the next-generation 6T40 GM Hydra-Matic transmission with reduced friction components over the previous generation.

A version of the vehicle (with 3.0L V6 engine mated to a six-speed automatic transmission) was unveiled at the 2010 Busan International Motor Show.

Redesigned front and rear fascias, new wheel designs, a reconfigurable eight-inch TFT LCD instrument cluster, semi-aniline leather seating, and radar- and camera-based safety features such as forward collision alert and side blind zone alert are among the most notable changes for this mid-cycle refresh.

For 2016, the LaCrosse added a new Sport Touring Edition which included unique 18" aluminum black pocket wheels, and a rear lip spoiler.

The platform switch and use of high-strength steels reduced weight by about 300 pounds (140 kg), despite slightly growing in length and width.

Since 2018, the LaCrosse came standard with an eAssist drivetrain, consisting of a mild hybrid 20-kilowatt (27 hp) electric and 2.5-liter Ecotec gasoline engine sending power to the front wheels through a 6-speed automatic transmission.

"[73] In addition, reviewers were critical of the sticker price on top-trim, heavily optioned models with Bloomberg saying "by the time you spend the $48,395 it costs to get the LaCrosse to this level, you're creeping into Audi/BMW/Mercedes territory.

"[74] The Buick LaCrosse was one of six vehicles GM discontinued after the 2019 model year amid a global restructuring effort.

The 2019 LaCrosse was available with a nine-speed Hydra-Matic automatic transmission with an average fuel consumption of 6.9 liters per 100 kilometers (34 miles per gallon).