The long-running E-Class slots between the entry-level C-Class sedan and the flagship S-Class sedan in the US model range. There are a large number of models to cover most needs with alphanumeric model names to indicate the powertrains within. A 268-bhp 3.5 L V6 powers the E350, whereas a 382-bhp V8 powers the E550. Both are fitted with a 7-speed automatic transmission. Customers can choose to add 4MATIC all-wheel-drive for all-weather traction. A sport appearance package adds body cladding and more aggressive wheels and tires. The ultimate E-Class sedan is the E65 AMG, a factory tuned beast with over 500 horsepower under the hood. Diesel engine options will return in 2010.

The Mercedes-Benz E-Class is redesigned for 2010. The edgier styling loses the rounded edges and headlamps that were once a staple of all Mercedes passenger cars. The new model is almost identical in size to the outgoing model. The E350 V6 model and E550 V8 model return with similar output to the prior model. Both offer RWD and 4MATIC AWD drivelines. A 7-speed automatic transmission is standard. The range topping E63 AMG sedan returns with 6.2L V8 that cranks out 518-bhp.