The second-generation Mercedes-Benz GL-Class (chassis code X166) debuted at the 2012 New York Auto Show. Up to 100 kg lighter than its predecessor through extensive use of aluminum hood and fender stampings, the X166 offered enhanced fuel efficiency, reduced wind noise, and superior ride comfort. Standard equipment encompassed three-row seating, AIRMATIC air suspension, and novel driver aids like Crosswind Assist.

Powertrains comprised the GL 350 BlueTEC 3.0-liter V6 turbodiesel and biturbo 4.7-liter V8 gasoline units powering the GL 450 and GL 500/550. This generation also introduced the high-performance GL 63 AMG equipped with a 5.5-liter twin-turbo V8 outputting 557 hp. In late 2015, a mid-cycle facelift accompanied the vehicle's renaming to the Mercedes-Benz GLS-Class.