The MDX was introduced on October 5, 2000[11] as a 2001 model, replacing the slow-selling U.S.-only body-on-frame SLX, based on the Isuzu Trooper.

To reduce drivetrain noise and increase fuel efficiency, the system runs as front wheel drive during normal cruising.

The second generation model's body has a wider track and longer wheelbase than the previous MDX.

This AWD system is one of the most advanced in its class, featuring an active rear differential often found on high performance cars, which somewhat mitigates the nose-heaviness of the MDX's traverse engine platform so it can dynamically compete with the longitudinal engine layout crossover SUVs.

The latter types of vehicles, such as the BMW X5 or Audi Q5, have a more balanced 50/50 front/rear distribution for better handling, but have less efficient packaging for passenger/cargo room.

[15][16] Like many Acura models, the MDX comes with a power sunroof, leather interior, and high-intensity discharge (Xenon) low-beam headlights.

However, AcuraLink real-time traffic reporting through XM NavTraffic is unavailable for Canadian MDX models.

In 2010, the MDX received a facelift adopting to Acura's new "Power Plenum" grille that debuted on its 2009 model year sedans.

An Advance Package became available that included Adaptive Cruise Control, blind spot monitor, Active Damper suspension, collision mitigation braking system, wider 7-spoked 19 inch wheels and tires, Premium Milano leather ventilated seats and auto leveling headlights.

Non-navigation equipped MDX models now have a backup camera monitor located in the rear-view mirror.

The interior reduced button clutter by adding a 7-inch touchscreen with haptic feedback, an additional 8-inch screen is also standard.

Advance package models include further noise reduction using a thicker carpet base layer and front fender liners.

According to Acura the exterior is more aerodynamic reducing drag by 16% with the new model lapping Nürburgring 8 seconds faster than its predecessor.

To reduce unsprung mass, the front suspension lower control arms are made from forged aluminum.

Acura states that after conducting a simulated IIHS 25% small offset frontal crash test the front doors will open with normal force.

[30] In 2018, for the 2019 model year, the Active Damper System is available for non-hybrids, the front seats feature 4-way power lumbar.

During the 2018 New York International Auto Show, alongside the debut of the third generation RDX, Acura announced the introduction of the A-Spec appearance package.

[35] The MDX became the flagship model of the Acura marque following the discontinuation of the RLX mid-size luxury sedan in June 2020.

The improved interior includes a 12.3-inch infotainment system and the Acura's first 12-inch digital full TFT instrument cluster, touch pad, 16-way power front seats with 3-memory positions, removable center second row seat, a removable double sided trunk floor with carpet and plastic, and more legroom and headroom compared to the third generation MDX.

The MDX also features an optional audio system with 16-speakers including four roof-mounted speakers and a foot sensor for Hands Free Access power tailgate release and closure when the key fob is nearby.

In the front, a double wishbone suspension with forged aluminum lower control arms, damper forks, and steering knuckles makes its way into the MDX along with more rigid cast-aluminum shock towers, larger front brake rotors and wider alloy wheels.

Plastic wheel well liners are replaced with fabric material and a repositioned air intake for easier access to both battery terminals.

The rear body is more rigid with suspension load paths passing into the C and D-pillars, allowing for towing capabilities.

The cooler kit is available as an accessory for the AWD models.The MDX facelift was revealed on April 9, 2024 for the 2025 model year.

Changes include updated exterior styling, new exterior colors, new alloy wheel designs, the touchpad controller has been replaced in favour of additional storage space and a wireless charging pad, a new 12.3-inch touchscreen infotainment system with Google built-in and the addition of new safety features such as AcuraWatch 360 system.