Sierra HD is the heavy-duty version of the Sierra 1500. It comes in 3/4-ton 2500 and 1-ton 3500 versions and is intended for commercial use. Three cab types are available: regular cab, extended cab with rear-hinged back half-doors, and a crew cab with four full-size front-hinged doors. All can be ordered with front bucket seats or a 40/20/40 split bench. The extended and crew cab models include a three-person rear bench. The regular cab comes with an 8-foot bed. Extended- and crew-cab models comes with either an 8-foot bed or a 6.5-foot bed. Chassis-cab and chassis cutaway models are also offered.

Both HD Sierra series are available with rear-wheel drive or 4WD that should not be left engaged on dry pavement but includes low-range gearing. An electronic-shift transfer case is standard on the 4WD SLT. All models have standard dual dashboard airbags and antilock 4-wheel disc brakes. Side-curtain airbags are not offered. Base engine is a 6.0-liter V8. Optional are an 8.1-liter V8 and 6.6-liter Duramax turbodiesel V8. The base engine teams with 5-speed manual transmission or optional 4-speed automatic with Tow/Haul mode. The two larger engines have a 6-speed manual or optional Allison 5-speed automatic with Engine Grade Braking, an electronic feature that makes an automatic downshift when descending steep slopes. Options include satellite radio, OnStar assistance system, a rear-seat entertainment system for Crew Cabs, and power-extending camper mirrors. Sierra HD is similar to Chevrolet Silverado HD.