Mercedes-Benz gave its E320 sedans and wagons a makeover for 2000, with styling updates to the cars' exteriors and interiors. Exterior upgrades included a new hood, grille, bumpers, and taillights, as well as new 16-inch wheels. Inside, the E320 vehicles received upgraded leather, carpeting, woodgrain trim, as well as a new instrument panel.

The cars received a number of new features as well, including the automaker's TeleAid emergency communication and assistance program, and the Electronic Stability Programming (ESP) anti-skid system.

Power for all models was provided by a 3.2-liter V6 engine that produced 221 horsepower. The engine was linked to a five-speed automatic transmission, which for 2000 came equipped with the new Touch Shift feature, enabling the driver to upshift and downshift by nudging the shift lever left or right.

The E320 was available in both sedan and wagon versions, as well as a sedan and wagon equipped with the 4Matic all-wheel-drive system, which improved handling, stability, and traction in all types of driving conditions.

Standard features for the E320 sedans and wagons included leather seats with power adjustment in the front, a two-zone automatic climate control system, dual front and side airbags, power windows, power exterior mirrors, cruise control, a leather-trimmed steering wheel and shift knob, a lighted entry system, trip computer, and AM/FM audio system with a cassette player. A CD player was available as an option. Other options included a sunroof, a parking alert system, and Mercedes' COMAND navigation system.

The E320 also came with anti-lock brakes, traction control, and an anti-theft alarm system.

Drivers noted that the E320 accelerated quickly and handled well. In addition, the new styling and interior upgrades were a hit with drivers. However, some drivers noted having electrical problems with the car.