Eventually the line was sold and went private to continue operating as a transatlantic shipping company that operated cargo services from 1921 to 1989, and ocean liners until 1969—most famously, United States.

United States Lines was the trade name of the United States Shipping Board's Emergency Fleet Corporation (EFC) organization created to operate the large German liners seized by the United States in 1917. By 1925 the corporation operated ex-German liners Leviathan, George Washington, America, Republic and the USSB built ships President Roosevelt and President Harding  in service between New York and Europe. On 15 November 1921 the line began operating from piers 3 and 4 at the USSB's Hoboken Terminal which had been the Hamburg America Line facilities in Hoboken, New Jersey seized by the United States and, during the war, operated by the Army as the Hoboken Port of Embarkation. The USSB engaged in advertising of the line and its ships through agencies using a "coupon" system to collect names and addresses of interested persons for direct mailings. All the line's funds were managed by the USSB Treasurer.

The line started with three ships from the tonnage of the failed United States Mail Steamship Company. One of the founders was Kermit Roosevelt, son of US President Theodore Roosevelt. Two of the ships, America and George Washington, were originally German vessels that had been seized during World War I and kept as reparations. Both America and George Washington made New York–Bremen runs, while Centennial State ran from New York to London.

The line became well known in the 1920s when two valiant historic rescues were made using their ships President Roosevelt in 1926 and America in 1929 by Captain George Fried.

More ships were acquired in 1922 and renamed after US presidents. The 52,000-ton Leviathan, formerly Vaterland and one of the largest liners in the world, was acquired in 1923.

Throughout the 1920s, the line accumulated debt, and in March 1929, the line was sold to P.W. Chapman Company, and reorganized as the "United States Lines Inc." of Delaware. The stock market crash made matters worse, and in 1931, the remaining ships were sold to "United States Lines Company" of Nevada. Later in 1931, United States Lines was acquired by the Roosevelt International Mercantile Marine Company, which had been formed earlier in the year from the merger of the Roosevelt Steamship Company and International Mercantile Marine Co.

In 1932, Manhattan, at a cost of approximately $21 million, became the first ship actually built for the line, followed the next year by Washington. In 1940, a new America joined them.

In 1932, United States Lines had offered to build a new passenger liner, called U.S. Express Liner, which would also double as a mail ship, and would dramatically decrease the time of delivery for trans-Atlantic mail by catapulting an aircraft when it was within range. Congress refused to give a guarantee on trans-Atlantic postal rates and it was never built.

During the 1930s, United States Lines' ailing parent company, Roosevelt International Mercantile Marine, began winding down its other operations and merging several of its divisions into United States Lines. United States Lines absorbed the American Line in 1932, the Baltimore Mail Line in 1937, and the American Merchant Line in 1938.