The S-Class is fitted as standard with the 7G-TRONIC 7-speed automatic transmission developed by Mercedes-Benz (not available for the S 600 or S 65 AMG). The seven gears make for smaller shifts in engine speed – which means that you’ll hardly notice the gear changes. Having seven gears also reduces the average engine speed and consequently fuel consumption. This automatic transmission is operated using the selector lever of the DIRECT SELECT transmission, which is located next to the steering wheel.

Apart from this, with the setup switch you can choose among three transmission settings: manual, comfort and sporty. The manual gearshifts are carried out with the gearshift paddles on the steering wheel – the way it's done in motorsport.

The S 600 and the S 65 AMG are equipped as standard with a 5-speed automatic transmission which works with electronic transmission regulation and is the perfect complement to the twelve-cylinder engine's characteristics. Gear changes are so fast and smooth that they are barely perceptible, while just the right amount of power is delivered for every situation. However, it is also possible to change gears manually.

In the S 65 AMG gears can be selected with the DIRECT SELECT selector lever and with the aid of the shift paddles on the AMG sports steering wheel – similar to the way it's done in Formula 1 cars.