[9] After leaving Western University, Andrew briefly worked at a lumber and coal business before joining T. Mellon & Sons as a full-time employee in 1873.

Mellon became a director of the company in 1891, and he and Richard played a major role in the establishment of aluminum factories in New Kensington, Pennsylvania, and Niagara Falls, New York.

Responding to the growing emphasis on naval power in the aftermath of the Spanish–American War, Mellon and Frick also became major shareholders in the New York Shipbuilding Corporation.

[31] The success of Mellon's financial empire and his varied investments made him, according to biographer David Cannadine, the "single most significant individual in the economic life and progress of western Pennsylvania" in the first decade of the 20th century.

[42] During the early 20th century, Mellon was dismayed by the rise of progressivism and the antitrust actions pursued by the presidential administrations of Theodore Roosevelt, William Howard Taft, and Woodrow Wilson.

[43] In the aftermath of World War I, he provided financial support to Henry Cabot Lodge and other Republicans in their successful campaign to prevent ratification of the Treaty of Versailles.

[45] By 1920, Mellon was little-known outside of banking circles, but his potential appointment to the cabinet received strong support from bankers and Pennsylvania Republican leaders like Knox, Senator Boies Penrose, and Governor Sproul.

Mellon was reluctant to enter public life due to concerns about privacy and a belief that his ownership of various businesses, including Old Overholt distillery, would be a political liability.

[51] His fortune continued to grow, and at one point in the 1920s he paid more in federal income tax than any other individual save John Rockefeller and Henry Ford.

[52] As Treasury Secretary, Mellon focused on balancing the budget and paying off World War I debts in the midst of the Depression of 1920–21; he was largely unconcerned with international affairs and economic matters such as the unemployment rate.

[57] He hoped that tax reform would encourage high earners to move their savings from tax-exempt state and municipal bonds to taxable, higher yield industrial stocks.

[60] He also strongly disapproved of a "Bonus Bill" passed by Congress that would provide for additional compensation to veterans of World War I, partly because he feared it would interfere with his plans to reduce debt and taxes.

[65] Congress also rejected Mellon's proposed constitutional amendment that would have barred the issuance of tax-exempt securities and, over Coolidge's veto, authorized a bonus to World War I veterans.

Mellon did, however, win one legislative victory, as he convinced Congress to create the Board of Tax Appeals to adjudicate disputes between taxpayers and the government.

[67] Mellon had originally planned to retire after one presidential term but decided to remain in the cabinet in the hope of presiding over the full enactment of his taxation proposals.

[76] In 1928, Mellon stated that "in no other nation, and at no other time in the history of the world, have so many people enjoyed such a high degree of prosperity or maintained a standard of living comparable to that which prevails throughout this country today.

[85] In 1928, responding to increasing fears of the dangers of speculation and a booming stock market, the Federal Reserve Board began raising interest rates.

Mellon had little sympathy for the speculators who lost their money, and he was philosophically opposed to an interventionist economic policy designed to address the stock market crash.

[89] Despite the optimism of Hoover and Mellon, in late 1930 the economy went into a deep slump, as gross national product declined dramatically, and numerous workers lost their jobs.

Again, following Hoover's lead, Mellon presided over the creation of the National Credit Association, a voluntary initiative among the larger banks that was designed to assist failing institutions.

[98] Mellon left office when Hoover's term ended in March 1933, returning to private life after twelve years of government service.

[105] Mellon believed that the various New Deal policies, including Social Security and unemployment insurance, undermined the free market system that had produced one of the largest economies in the world.

Aside from banking reform, other New Deal policies, including regulations on utilities and coal mines and laws designed to promote labor unions, also affected Mellon's business empire.

[110] In response to accusations levied by Republican Congressman Louis Thomas McFadden of Pennsylvania in early 1933, Attorney General Homer Cummings began an inquiry into Mellon's tax history.

Secretary of the Treasury Henry Morgenthau Jr. stated that Mellon had lived through "an epoch in the economic history of the nation, and his passing takes one of the most important industrial and financial figures of our time.

[128] In the 1920s, while Mellon served as Secretary of the Treasury, Ailsa was courted by several influential men, including Otto Christian Archibald von Bismarck, Robert Horne, and Gelasio Caetani.

Mellon also served as an alumni president[134] and trustee[135] of the University of Pittsburgh, and made several major donations to the school, including the land on which the Cathedral of Learning and Heinz Chapel were constructed.

Andrew W. Mellon appears in the HBO drama series Boardwalk Empire, in the fifth, eighth and twelfth episodes of the third season, in his capacity as Secretary of the Treasury.

In the alternate history/time travel story "A Slip in Time" by S. M. Stirling,[149] featuring a history in which the First World War was avoided and the Austro-Hungarian Empire survived, Andrew Mellon was the President of the United States in 1926.

Mellon is the subject of three unflattering chapters in Matt Stoller's 2019 book, Goliath: The 100 Year War Between Monopoly Power and Democracy, which recounts efforts by populists in Washington (namely, Congressman Wright Patman; Roosevelt administration lawyer Robert H. Jackson; and Ferdinand Pecora, attorney for the Senate Banking Committee) to expose Mellon's crimes and abuse of power for personal gain.