The seventh-generation Mercedes-Benz E-Class (W211) debuted in January 2002 at the Brussels Motor Show. Evolving the four-eyed front-end design with sleek, swept-back lines, the W211 was offered as a sedan (W211) and estate (S211). Technological innovations included Sensotronic Brake Control (SBC) electro-hydraulic brakes, AIRMATIC DC dual-control air suspension, active dynamic seats with massage functions, and panoramic glass roofs.

Engine choices included supercharged M271 four-cylinder engines, modern DOHC V6 and V8 gasoline units (M272, M273), and smooth CDI turbo-diesels ranging from 2.1 liters up to the powerful 4.0-liter V8 in the E 420 CDI. The dual-fuel natural gas E 200 NGT catered to eco-minded municipal fleets. AMG models set class performance records with the supercharged V8 E 55 AMG producing 476 hp, later succeeded by the high-revving naturally aspirated 6.2-liter V8 E 63 AMG generating 514 hp. A major 2006 facelift replaced the Sensotronic Brake Control system with conventional adaptive hydraulics, added PRE-SAFE predictive occupant protection, introduced the 7G-Tronic seven-speed automatic transmission, and recalibrated steering directness for sharper driving dynamics.