A big-block engine, variants were produced in 305-, 351-, 401-, and 478-cubic-inch (5.0, 5.8, 6.6, and 7.8 liters respectively) displacements, with considerable parts commonality.

During the latter years of production, 379-and-432-cubic-inch (6.2 and 7.1 L) versions with enlarged crankshaft journals were manufactured as well.

GMC produced a 637-cubic-inch (10.4 L) 60° V8 with a single camshaft using the same general layout (bore and stroke) as the 478 V6.

The 637 V8 was the largest-displacement production gasoline V8 ever made for highway trucks.

The largest engine derived from the series was a 702-cubic-inch (11.5 L) "Twin Six" V12, which had a unique block and crankshaft, but shared many exterior parts with the 351.

All versions of the GMC V6 used a six-throw crankshaft, which when combined with the 60 degree included cylinder angle, produced a smooth-running engine without any need for a balance shaft.

Spark plugs were located on the inboard side of the cylinder heads and were accessed from the top of the engine.

This position allowed for shorter spark-plug wires and kept the spark plugs away from the hot exhaust manifolds, something which was emphasized in sales literature.

These GMC V6 engines were noted for durability, ease of maintenance, and strong low-end torque.

[11] The 305A was equipped with a single barrel carburetor and produced 150 hp (112 kW) gross at 3600 RPM and 260 lb⋅ft (353 N⋅m) gross at 1600 RPM (measured without air cleaner or accessories in an ideal environment).

[12] The 305 was GMC's standard pickup truck and Suburban engine from 1960 to 1969.

The 305B and 305C (a 305B with a different manifold and carburetor) were used in 4000 and 5000 series trucks; the 305B was dropped in 1962 while the 305C continued to 1974.

It was the largest-displacement production gasoline V8 ever made for highway trucks.

It was its own separate engine design, based on a single block casting,[19] which had four exhaust manifolds, two carburetors and intake manifolds, and two distributor caps driven by a single distributor drive,[19] plus other parts from the 351 V6.

[23] The naturally aspirated GMC four-stroke diesel engines were added to the General Motors truck line for the 1965 model year.

[10]: 34  Although they shared similar displacement, bore, and stroke dimensions with the gasoline engines, very few parts were the same.