Samuel Gompers was born on January 27, 1850, in London, England into a Jewish family that originally hailed from Amsterdam. When he was six, Samuel was sent to the Jewish Free School, where he received a basic education. His elementary school career was brief, however, since a mere three months after his tenth birthday Gompers was removed from school and sent to work as an apprentice cigar maker to help earn money for his impoverished family.

Owing to dire financial straits, the Gompers family immigrated to the United States in 1863, settling in the Lower East Side of Manhattan in New York City. Gompers' Father was engaged in the manufacture of cigars at home, assisted for the first year and half by Samuel. In his free time, the young teenager formed a debate club with his friends, an activity that provided practical experience in public speaking and parliamentary procedure. The club drew Gompers into contact with other upwardly mobile young men of the city, including a young Irish-American named Peter J. McGuire, who later would play a large role in the AFL.

In 1864, at the age of 14, Gompers joined and became involved in the activities of the Cigar Makers Local Union No. 15, the English-speaking union of cigar makers in New York City. Gompers later recounted his days as a cigar maker at the bench in detail, emphasizing the place of craftsmanship in the production process:

In 1873, Gompers moved to the cigar maker David Hirsch & Company, a "high-class shop where only the most skilled workmen were employed". Gompers later called this change of employers "one of the most important changes in my life", for at Hirsch's—a union shop operated by an émigré German socialist—Gompers came into contact with an array of German-speaking cigar makers—"men of keener mentality and wider thought than any I had met before," he recalled. Gompers learned German and absorbed many of the ideas of his shop mates, developing a particular admiration for the ideas of the former secretary of the International Workingmen's Association, Karl Laurrell. Laurrell took Gompers under his wing, challenging his more simplistic ideas and urging Gompers to put his faith in the organized economic movement of trade unionism rather than the socialist political movement.

Gompers was elected President of Cigar Makers' International Union Local 144 in 1875.

As was the case with other unions of the day, the Cigar Maker's Union nearly collapsed in the financial crisis of 1877, in which unemployment skyrocketed and ready availability of desperate workers willing to labor for subsistence wages put pressure upon the gains in wages and the shortening of hours achieved in union shops. Gompers and his friend Adolph Strasser used Local 144 as a base to rebuild the Cigar Makers' Union, introducing a high dues structure and implementing programs to pay out-of-work benefits, sick benefits, and death benefits for union members in good standing.

Gompers helped found the Federation of Organized Trades and Labor Unions in 1881 as a coalition of like-minded unions. In 1886 it was reorganized into the American Federation of Labor, with Gompers as its President. With the exception of one year, 1895, he would remain President of the organization until his death.

Gompers, like most labor Leaders, opposed unrestricted immigration from Europe because it lowered wages. He strongly opposed all immigration from Asia because it lowered wages and, in his judgement, represented an alien culture that could not be assimilated easily into that of the U.S. He and the AFL strongly supported the Chinese Exclusion Act of 1882 that banned the immigration of Chinese. The AFL was instrumental in passing immigration restriction laws from the 1890s to the 1920s, such as the 1921 Emergency Quota Act and the Immigration Act of 1924, and seeing that they were strictly enforced. At least one study concludes that the link between the AFL and the Democratic Party rested in large part on immigration issues, as the owners of large corporations wanted more immigration and thus, supported the Republican Party. Other scholars have seriously questioned this conclusion, arguing it oversimplifies the politics and unity of labor Leaders and the major parties. As one reviewer argued in The Journal of American History, major Republican Leaders, such as President william McKinley and Senator Mark Hanna, made pro-labor statements, many unions supported their own independent labor parties, and unity within the AFL was never so extensive as claimed.

He was elected second vice President of the Cigar Makers' International Union in 1886, and first vice President in 1896. Despite the commitment of time and Energy entailed by his place as head of the American Federation of Labor, Gompers remained first vice President of the Cigar Makers until his death in December 1924.

During a severe period of national economic recession in the early 1890s, labor unrest was at its height. A volatile situation in Chicago in August 1893 caused the city’s then mayor, Carter Henry Harrison, to warn that the preponderance of the unemployed would lead to riots that would “shake the country”, unless Congress interceded. In late August 1893, Gompers addressed 25,000 unemployed workers who had massed on the shore of Lake Michigan. As reported in the Chicago Tribune on August 31, Gompers inveighed against the controllers of capital and the titans of industry and Finance. “Why should the wealth of the country be stored in banks and elevators while the idle workman wanders homeless about the streets and the idle loafers who hoard the gold only to spend it on riotous living are rolling about in fine carriages from which they look out on peaceful meetings and call them riots?”

Gompers led the anti-Socialist faction inside the AFL, losing to them only once, in 1894. He argued that socialists believed workers and unions could never co-exist with Business interests and wanted to use the labor unions to advance their more radical political causes. By 1920 Gompers had largely marginalized Socialist influence to a few unions, notably coal miners and the needle trades.

Gompers began his labor career familiar with, and sympathetic to, Georgism and the precepts of socialism, but gradually adopted a more conservative approach to labor relations. Labor Historian Melvyn Dubofsky has written, "By 1896 Gompers and the AFL were moving to make their peace with Capitalism and the American system... Although the AFL had once preached the inevitability of class conflict and the need to abolish 'wage slavery', it slowly and almost imperceptibly began to proclaim the virtues of class harmony and the possibilities of a more benevolent Capitalism." For Example, Alex Heron attributes the following quote to Gompers: "The greatest crime an employer can perpetrate on his employees is to fail to operate at a profit". Gompers began to take a neutral stance in politics after the failure of the efforts to elect Henry George as mayor of New York, but Gompers remained a Single Tax Georgist later in life.

Gompers, who had ties with the Cuban cigar workers in the U.S., called for American intervention in Cuba; he supported the resulting war with Spain in 1898. After the war, however, he joined the Anti-Imperialist League to oppose President william McKinley's plan to annex the Philippines. Mandel (1963) argues that his Anti-imperialism was based on opportunistic fears of threats to labor's status from low-paid offshore workers and was founded on a sense of racial superiority to the peoples of the Philippines.

Under Gompers's tutelage, the AFL coalition gradually gained strength, undermining the position previously held by the Knights of Labor, which as a result, had almost vanished by 1900. He was nearly jailed in 1911 for publishing, with John Mitchell, a boycott list, but the Supreme Court overturned the sentence in Gompers v. Buck's Stove and Range Co..

Gompers's trade union philosophy and his devotion to collective bargaining with Business proved to be too conservative for more radical Leaders, such as Ed Boyce, President of the Western Federation of Miners (WFM), and, later, WFM secretary-treasurer Bill Haywood. In 1905, Haywood and the WFM helped to establish the Industrial Workers of the World (IWW), whose members were known as Wobblies, with the goal of organizing the entire working class. The IWW's long-term goal was to supplant capitalism with a workers' commonwealth. Nonetheless, when government abuses against the Leaders of the WFM seemed too egregious, Gompers relented and offered assistance.

Gompers was a leading Freemason, reaching the 32º in the Scottish Rite Valley of Washington in 1906. In 1920 he wrote, "In my Masonic life I have visited lodges in many lands, and I have learned that Freemasonry in many countries, particularly in Latin countries, is the principal means whereby freedom of conscience, of thought, and expression is preserved."

During World War I Gompers was a strong supporter of the war effort. He was appointed by President Wilson to the Council of National Defense, where he chaired the Labor Advisory Board. He attended the Paris Peace Conference in 1919 as an official advisor on labor issues.

Gompers and his AFL unions vigorously fought the IWW in the U.S. and in Latin America, as a disruptive dual union that tried harder to destroy capitalism than to help workers. He cooperated with widespread government arrests of union Leaders for the IWW's militant opposition to the World War. He said, "the IWW's...are exactly what the Bolsheviki are in Russia, and we have seen what the IWW Bolsheviki in Russia have done for the working people." The IWW was practically defunct by 1920.

Gompers' health went into serious decline starting in February 1923, when a serious bout of influenza sent him to the hospital, sidelining him from work for six weeks. No sooner had he recovered from the influenza, than he was stricken by a case of bronchitis that laid him low again. By June 1924 Gompers, who suffered from diabetes, could no longer walk without assistance, and he was hospitalized again, this time suffering from congestive heart failure and uremia.

He collapsed in Mexico City on Saturday, December 6, 1924, while attending a meeting of the Pan-American Federation of Labor. It was recognized that his condition was critical and that he might not survive for long. Gompers expressed the Desire to die on American soil and he was placed aboard a special train that sped toward the border. He died in San Antonio, Texas. Gompers was buried at the Sleepy Hollow Cemetery in Sleepy Hollow, New York. Gompers is buried only a few yards away from industrialist Andrew Carnegie, another important figure of industry in the Gilded Age.

Gompers is the subject of statuary in several major American cities. A bronze monument honoring Gompers by the Sculptor Robert Aitken is in Gompers Square on Massachusetts Avenue in Washington, D.C.. On September 3, 2007, a life-size statue of Gompers was unveiled at Gompers Park, named after the labor leader in 1929, on the North West side of Chicago. This is the first statue of a labor leader in Chicago. Local unions throughout Chicago donated their time and money to build the monument. A U.S. Navy support ship and an entire class of U.S. Navy destroyer tenders were named for Gompers. The Samuel Gompers Houses, a public housing development on the Lower East Side of New York, is named in his honor. There are schools named for Gompers in Philadelphia, Pennsylvania, Madison, Wisconsin, and Phoenix, Arizona.

Gompers's philosophy of labor unions centered on economic ends for workers, such as higher wages, shorter hours, and safe working conditions so that they could enjoy an "American" standard of living—a decent home, decent food and clothing, and money enough to educate their children. He thought economic organization was the most direct way to achieve these improvements, but he did encourage union members to participate in politics and to vote with their economic interests in mind.