The GM "Buffalo" bus models were strongly influenced by the PD-4501 Scenicruiser, a model GM manufactured exclusively for Greyhound Lines between 1954 and 1956.

The Scenicruiser was a bi-level model, with a lower level at the front containing the driving console and 10 seats behind it, and with an upper level containing seating for 33. This allowed for a huge baggage compartment beneath the raised second level, and also provided a 360-degree view for upper level passengers. A lavatory was located at the rear of the first level. Scenicruisers were equipped with air-ride suspension which utilized an air bag at each wheel, and were air-conditioned. Later, on the Model PD-4106 incorporated a new design by having the air-conditioning unit powered from an engine-mounted compressor, a patented V-drive engine-transmission design, and the 6V71 or 8V71 Detroit Diesel engine.

As Scenicruisers became a familiar sight around the United States, and in advertising, competing bus companies including members of the National Trailways Bus System sought a vehicle to compete with it. One of the product designs developed in response to this market demand was the GM "Buffalo" bus, so nick-named owing to the hump-back style of the roofline. Unlike the Scenicruiser, these models were available for sale to all operators. In fact, Greyhound eventually purchased a few of them; the last GM bus purchased by Greyhound was a 1967 PD-4107. Many features such as the split-level design and the revisions introduced in the PD-4106 model were included in the Buffalo bus. In 1966, GM introduced the PD-4107. Also known informally as "decks", these buses were similar in some ways to the Scenicruiser design, but had a larger "second level" with the first level reduced, and the lavatory was located at the rear. The 4107 was 35-foot (11 m) in length, and nominally (without lavatory) would seat 41 passengers (38 or 39 with lavatory). In 1968, the PD-4903 was introduced, a 40-foot (12 m) long version of the 4107 which nominally would seat 49 passengers (46 or 47 with lavatory). The PD-4903 was the first GM bus to use a 24 volt electrical system and was 40 feet long with a third luggage bay. For states with lower axle load limits, a factory option used the third bay to hold a retractable two-tire axle.In the so-called "Buffalo" design, the driver sat higher than in the Scenicruiser, but the passenger compartment was no higher than the Scenicruiser's upper deck, so the Buffalo was not actually a double decker. The difference in the height of the front and rear roof was approximately one foot, giving a sleeker, more aerodynamic shape.These product lines used an airplane-like stressed-skin construction in which an aluminum riveted skin supports the weight of the bus, while a rigid wooden floor platform kept the buses structural shape. The engine cradle was hung off the back framing of the roof.GM's Buffalo models were powered by the eight cylinder Detroit Diesel 71-series two-cycle (with a super-charger) diesel engines known as the 8V71. GM buses used a unique "V-drive" configuration with a transverse mounted engine. The transmission angled off at a 45-or-so degree angle to connect to the rear axle. The left hand rotating engines were canted backwards for maintenance access; in fact the only major components not accessible from outside the bus were the right-hand exhaust manifold and the starter, which were accessible from underneath and via access panels under the rear passenger seat. The entire engine–transmission–radiator assembly was mounted on a cradle which could quickly be removed and replaced for maintenance, allowing the bus to rapidly return to revenue service while leaving the powertrain in the shop for repairs. The original buses had a 4-speed non-synchronized manual transmission with a solenoid reverse. Later in production, an Allison automatic transmission version was offered.The manual transmission 4107 and 4903 models were notorious for being difficult to shift through the gears, often making loud, grinding noises that tended to upset the passengers. the technique known as "double-clutching" reduced these embarrassing noises, but even the most skilled driver would occasionally have problems, especially when changing buses (and/or powertrains) gave them an unfamiliar feel to clutch and shifter. In 1970, design improvements came with the updated versions, PD-4108 (35 ft) and PD-4905 (40 ft) both with a 24-volt electrical system. The driver's controls were updated for both. The biggest complaint about the 4905 and 4903, from the drivers’ point of view, was that the extra 5 feet (1.5 m) of length was all between the front and rear axles. It was very easy to scrape the baggage compartment doors on tight turns. The 4905s looked just like 4108s but with three baggage compartments. Some 4905s had a tag axle, with a single extra wheel on each side, located in the third baggage compartment, but it was forward of the drive axle, so turning radius was not affected.