In 1901, Max Grabowski established a company called the "Rapid Motor Vehicle Company", which developed some of the earliest commercial trucks ever designed. The trucks utilized one-cylinder engines. In 1909, the company was purchased by General Motors to form the basis for the General Motors Truck Company, from which GMC Truck was derived.

Another independent manufacturer purchased by GM that same year was Reliance Motor Car Company. Rapid & Reliance were merged in 1911, and in 1912 the marque "GMC Truck" was first shown at the New York International Auto Show. Some 22,000 trucks were produced that year, though GMC's contribution to that total was a mere 372 units.

In 1916, a GMC Truck crossed the country from Seattle to New York City in thirty days, and in 1926, a 2-ton GMC truck was driven from New York to San Francisco in 5 days and 30 minutes. During the Second World War, GMC Truck produced 600,000 trucks for use by the U.S. military.

In 1925, GM purchased the controlling interest in Yellow Coach, a bus manufacturer based in Chicago, Illinois which was founded by John D. Hertz. After purchasing the remaining portion in 1943, GM renamed it GM Truck and Coach Division, and it manufactured transit and inter-urban buses in Canada and the United States until the 1980s. GM faced increased competition in the late 1970s and 1980s and stopped producing buses soon after. In 1987, GMC later sold their bus models to Transportation Manufacturing Corporation (also under Motor Coach Industries in Canada) and later NovaBus.

In 2002, GMC released a book entitled, GMC: The First 100 Years, that explained the company's complete history.

GMC currently manufactures SUVs, pickup trucks, vans, light-duty trucks, and medium-duty trucks. In the past, GMC also produced fire trucks, ambulances, heavy-duty trucks, military vehicles, motorhomes, and transit buses.

Although GMC and Chevrolet trucks are almost identical, their differences have varied throughout the years. Traditionally, the GMC has had different trim from the Chevrolet (i.e. grill, emblems, etc.), larger engine options, and a generally higher price. Between 1962 and 1972, most GMC vehicles were equipped with quad-headlights, while their Chevrolet counterparts were equipped with dual-headlights. Starting in 1973, with GM’s introduction of the new "rounded line" series trucks, GMC and Chevrolet trucks became even more similar, ending production of GMC’s quad-headlight models, and setting the standard for the Chevrolet/GMC line of trucks for over thirty years. During this period, the sister models of the two companies (Silverado/Sierra, Blazer/Jimmy, Tahoe/Yukon, etc) shared everything except trims and price. GM has recently begun a divergence in design between the two lines with the 2007 model Silverados and Sierras, which have slight differences in the shapes of their body panels and overall looks.

Today, for the most part, GMC offers the same trucks available under the Chevrolet brand. A Sprint, for example, was a rebadged Chevrolet El Camino, the Sierra is a rebadged Chevrolet Silverado, etc. In the United States GMC is usually sold by dealers in combination with Buick or Pontiac, typically at lower volumes than the equivalent Chevrolet trucks. GMC trucks are positioned as the Professional Grade versions of the equivalent Chevrolet vehicles. GMC's trucks, vans, and SUVs offer more options and standard features than Chevrolet, while Chevrolet is often offered as an entry-level car. In Canada, GMC is sold by Pontiac-Buick-GMC dealerships, usually at volumes equivalent or greater than the comparable Chevrolet trucks.

In 2007, GMC introduced the Acadia, a crossover SUV, which is the company's first unibody vehicle. The 2007 model year equivalent model from Saturn is the Outlook.

In 2009, GMC will introduce the all-new Terrain, a mid-size crossover SUV based on GM's Theta platform which will slot below the Acadia as GMC's smallest crossover. Its predecessor, the GMT-360 based Envoy, will be discontinued in 2008.