The first two Buick automobiles were made in 1899 and 1900 at the "Buick Auto-Vim and Power Company" by chief engineer Walter Marr, but company owner David Dunbar Buick was reluctant to begin making automobiles, being satisfied with stationary and marine engine production, so Marr left Buick in 1901 to found his own automobile company under his own name. His replacement was Eugene Richard, who applied for a patent in 1902 for Marr's valve-in-head (overhead valve) engine, which patent, number 771,095, was awarded to Richard in the name of Buick in 1904. In 1903, the third Buick automobile was made, this time by Richard, but in 1904 Buick, whose company was now called "Buick Motor Company", moved from Detroit to Flint, Michigan, and Richard stayed behind. Marr was rehired in Flint as chief engineer, to begin making automobiles in production. That year, 37 Buick automobiles were made, production increasing to 750 in 1905, 1,400 in 1906, 4,641 in 1907, and 8,820 in 1908, taking the number one spot away from close competitors Ford, Maxwell and Olds Motor Works. Buick proclaimed themselves the largest car manufacturer in the world this year.

David Buick incorporated his company as the Buick Motor Company on May 19, 1903, in Detroit, Michigan. Buick had been financed by a friend and fellow automobile enthusiast, Benjamin Briscoe, who in September 1903 sold control of the business to James H. Whiting, of Flint Wagon Works, in Flint, Michigan. Whiting moved Buick to Flint, to a location across the street from his factory, with the idea of adding Buick's engines to his wagons. David Buick stayed on as a manager and re-hired Walter Marr as chief engineer. The engine Buick and Marr developed for this automobile was a two-cylinder valve-in-head engine of 159 cubic inches, with each cylinder horizontal and opposed to the other by 180 degrees.

Whiting built only a few automobiles in 1904, the Model B, before running out of operating capital, causing him to bring in William C. Durant that year as a controlling investor. Durant built a few more model B's in 1904, stepped up production for the model C in 1905, and spent the next four years turning Buick into the biggest-selling automobile brand in the US.

During the 19th century, Durant had made his fortune as co-owner, also in Flint, with Josiah Dallas Dort, of the Durant-Dort Carriage Company, which by 1904 was the largest carriage-making company in the country and one of the largest in the world. Durant moved most Buick production to the former Durant-Dort Imperial Wheel plant in Jackson, Michigan in 1905. Buick continued car production in Jackson through 1907, when Factory #1 was completed in Flint. The Jackson plant continued production with Buick trucks through 1912. David Buick sold his stock upon departure in 1906, making him a wealthy man, but he died in modest circumstances 25 years later. In 1907, Durant agreed to supply motors to R. S. McLaughlin in Canada, an automaker, and in 1908 he founded General Motors.

Between 1899 and 1902, two prototype vehicles were builT in Detroit, Michigan by Walter Lorenzo Marr. Some documentation exists of the 1901 or 1902 prototype with tiller steering similar to the Oldsmobile Curved Dash.

In mid-1904, another prototype was constructed for an endurance run, which convinced Whiting to authorize the production of the first models offered to the public. The architecture of this prototype was the basis for the Model B.

The first Buick made for sale, the 1904 horizontally opposed 2-cylinder engine Model B, was built in Flint, Michigan at a re-purposed factory that was known as the Flint Wagon Works. There were 37 Buicks made that year, none of which survive. There are, however, two replicas in existence: the 1904 endurance car, at the Buick Gallery & Research Center in Flint, and a Model B assembled by an enthusiast in California for the division's 100th anniversary. Both of these vehicles use various parts from Buicks of that early era, as well as fabricated parts. These vehicles were each constructed with the two known surviving 1904 engines.

The early success of Buick is attributed mainly to what it called the valve-in-head engine, now known as the overhead valve (OHV), engine patented by Eugene Richard and developed by Richard, Buick, and Marr. The Model F had a two-cylinder engine, an 87-inch wheelbase, and weighed 1,800 lbs. The creation of General Motors is attributed mainly to the success of Buick, so it can be said Marr and Richard's designs directly led to GM. The power train and chassis architecture introduced on the Model B was continued through the 1909 Model F.

The Model F was similar to the Model G, a lower-priced two-seat roadster, produced from 1906 until 1909. Both the F and G were powered by a 159 cu in (2.6 L) two-cylinder 159 engine producing 22 hp (16 kW; 22 PS) along with a 2-speed transmission as well as mechanical brakes on the rear wheels.

The flat-twin engine is inherently balanced, with torque presented to the chassis in a longitudinal manner. The engine was mounted amidships.

Billy Durant was a promoter, and Buick soon became the largest carmaker in America. Durant embarked on a series of corporate acquisitions, calling the new firm General Motors. At first, the manufacturers comprising General Motors competed against each other, but Durant ended that. He wanted each General Motors division to target one class of buyers. Buick was positioned below the Cadillac brand. To save on resources, Buick vehicles shared a common platform, called the GM A platform, that was shared with Chevrolet, Oakland, Oldsmobile, and Cadillac.

At first, Buick followed the likes of Napier in automobile racing, winning the first-ever race held at Indianapolis Motor Speedway.