Ford sold the Quadricycle to construct other cars and improve his prototype. For the next seven years, investors helped him found the Detroit Car Company (eventually the Henry Ford Corporation) in 1899. Ford quit his namesake company in 1902 because his partners, eager to sell passenger cars, were disillusioned with his incessant urge to improve. After his left, it became Cadillac Motor Vehicle Corporation. Ford Motor Corporation was founded the next year. The Model A, a two-cylinder, eight-horsepower car, was produced at a Mack Avenue plant in Detroit a month after Ford Motor Company was founded. At the time, two or three people hand-assembled a few cars per day using parts ordered from other companies. The Model T, introduced in October 1908, was Ford's attempt to make a reliable, affordable car.

The Model T, nicknamed "Tin Lizzie," was a hit, and Ford had more orders than it could fill. He used massive production plants, interchangeable parts, and the moving assembly line to transform American industry. Mass production reduced car manufacture time and cost. In 1914, Ford raised his workers' eight-hour daily wage to $5 from $2.34 for nine hours, setting an industry norm. By 1918, 50% of American automobiles were Model Ts. Ford named his son Edsel president of Ford Motor Company in 1919, but he retained full control. By 1920, Henry Ford bought out all minority owners after a legal struggle with brothers Horace and John Dodge. Ford transferred production to his huge Dearborn, Michigan, industrial complex on the River Rouge in 1927. The plant had a glass factory, steel mill, assembly line, and all other automotive production components. Ford discontinued the Model T and introduced the Model A, which had superior horsepower and brakes. The world's largest automaker, Ford Motor Company, had built 15 million Model Ts by then. Ford expanded globally.

The Model A was discontinued in 1931 after being outsold by Chevrolet (GM) and Plymouth (Chrysler). By 1936, Ford had fallen to third in vehicle sales despite introducing the first V-8 engine in 1932. Ford fought the United Automobile Workers (UAW) even after his competitors did, despite his progressive minimum wage policy. The National Labor Relations Board ordered Ford to stop interfering with union organization after the 1937 "Battle of the Overpass" at the Rouge factory between Ford security and UAW organizers. Ford Motor Company signed its first UAW contract in 1941, although Henry Ford pondered closing the company to avoid it. Ford was criticized for his political views, starting with his opposition to World War One. In 1918, he narrowly lost a U.S. Senate race marred by personal assaults. The World Jew, a four-volume collection of Ford's anti-Semitic writings from the Dearborn Independent, a local newspaper he bought in 1918. Though he later abandoned the essays and sold the paper, he admired Adolf Hitler and Germany and accepted the Nazi regime's highest foreigner honor, the Grand Cross of the German Eagle, in 1938. After Edsel Ford died in 1943, Henry Ford briefly took control Ford Motor Company before passing it to his grandson, Henry Ford II, in 1945. At 83, he died in Dearborn.