Standard GP40-2 production totalled 861 units, with 817 built for U.S. railroads, and 44 for Mexican railroads. In addition, three GP40P-2s, passenger versions of the GP40-2, were built for Southern Pacific in 1974, and 279 GP40-2L(W) and GP40-2(W) units, equipped with wide-nosed cabs, were built by General Motors Diesel (GMD), for Canadian National and GO Transit between 1974 and 1976. Of the CN units, 233 were built with a taller and lighter frame to allow for a larger fuel tank. These units were officially classified GP40-2L but are commonly referred to as GP40-2L(W). The balance of CN's fleet, 35 units, and the 11 unit GO Transit fleet, used standard frames and smaller fuel tanks; they are often referred to as GP40-2(W) but are classified as GP40-2. Total production of the GP40-2 and its variations totalled 1,143 units.
Although the GP40-2 was a sales success, it sold fewer units than the earlier GP40 and the contemporary GP38-2 and SD40-2 models. The popularity of high-horsepower 4-axle diesels began to decline with the GP40-2, with 6-axle models gaining in popularity for their superior low-speed lugging performance.
Like the SD40-2 the GP40-2 has a reputation for reliability, and many are still in use. Changes such as the modular electronics system improved reliability over the GP40. Their high power-per-axle rating suited them to high-speed service rather than low-speed drag freights.
With the usual 62:15 gearing (65-70 mph maximum) EMD rated the GP40-2 at 55,400 lb continuous tractive effort; for compatibility with other units, most (all?) had the PF21 module that reduced horsepower below 23 mph, bringing the minimum continuous speed down to 11 mph.