The first generation Q45 came to market in 1989 as a 1990 model with a high-output 4.5 L VH45DE DOHC 32V V8 engine rated at 278 hp (207 kW) and 292 lb⋅ft (396 N⋅m) in North American trim.

At launch, the US$38,000 (equivalent to $93,000 in 2023) sedan had a single option, the Touring Package, which added Nissan's Super HICAS four-wheel steering system, a decklid spoiler, and alloy wheels.

However, the Q45 did not achieve similar sales volumes, which was attributed to the car's unconventional styling, particularly the grille and lack of interior woodgrain or chrome trim.

[19] The suspension provides an active response to road features up to approximately 3 Hz, a limit imposed by minimizing the size of the additional hardware and power losses required to pressurize the hydraulic accumulator;[19] it added 202 lb (92 kg) and reduced fuel economy by 10%.

[19] Mercedes-Benz also developed a similar system named Active Body Control, which was introduced a decade later in 1999 on the C215 CL-Class.

[14] Standard equipment included a Bose sound system, leather interior, power adjustable front passenger seats with two position memory feature that also electrically adjusted the steering wheel, exterior mirrors, one-touch power windows, digital climate control, and keyless entry system.

For most of its vehicles, Infiniti uses a naming convention that combined a letter indicating the series or market position, followed by a two-digit number for engine displacement; for instance, the first generation Q45 (G50) name designates the flagship (Q-series) followed by 45 for its 4.5-liter V8; the second-generation Q45 was an exception (as was the QX4, derived from the contemporary Nissan Pathfinder), as it used a smaller 252 cu in (4.1 L) VH41DE engine.

Despite the shorter wheelbase in the Y33 compared to the G50, rear legroom increased by 3.9 in (99 mm); however, the trunk was faulted by owners as being small, with a volume of 12.6 cu ft (360 L).

[26] As Edmunds noted for the 1997 model year, "The Q45 no longer has aspirations to be a sport sedan, its prime duties now are interstate cruising.

The package included all features of the Q45t model along with "Anniversary Edition" markings on the tailgate badge, ignition key, front seat embossing and floor mats as well as genuine wood trim, wood tone/leather steering wheel, special bright machine finish 17-inch performance wheels and exclusive body color door handles.

[31] Introduced at the 2000 New York Auto Show,[35] the third generation Q45 (F50) was, like the preceding Q45 (Y33), based on the JDM Cima and was powered by a new twin-cam 4.5 L VK45DE V8 engine using a 5-speed automatic transmission with overdrive.

At its introduction, Brock Yates, writing for Car and Driver, compared the third generation Q45 against close market competitors, calling it a "superbly refined, comfortable, and distinctive machine.

The center console features two sizes of concealed cup holders and a hatch under the armrest and a second, deeper compartment.

[44] The 2002 Q45 was the first vehicle ever to offer voice-controlled navigation and a reverse parking camera outside Japan, following the JDM 1991 Toyota Soarer.

[39] The 2003 model received a revised security system, numerically higher final drive ratio (for better acceleration - decreased highway fuel economy), reprogrammed TCU, and a mid-year satellite radio option.

Infiniti discontinued marketing the Q45 in the USA after model year 2006, its flagship position assumed by a newly redesigned Infiniti M35/45, an mid-luxury (executive) car shorter in length than the Q45, though with greater interior room and performance, as well as featuring a rear multilink suspension and front double wishbone.

According to Mark Igo, the general manager of Infiniti North America, "the new Q will make the brand better, but it is questionable whether it will be very profitable".