Fairbanks delivered the keynote address at the 1896 Republican National Convention and won election to the Senate the following year.

[1] In the Senate, he became an advisor to President William McKinley and served on a commission that helped settle the Alaska boundary dispute.

[3] Fairbanks's first position was as an agent of the Associated Press in Pittsburgh, Pennsylvania, reporting on political rallies for Horace Greeley during the 1872 presidential election.

With the assistance of his uncle, Charles W. Smith, whose connections had helped him obtain the position, Fairbanks was able to become a railroad financier and served as counsel for millionaire Jay Gould.

At the 1896 Republican National Convention, Fairbanks was both temporary chairman and keynote speaker, further raising his public profile.

In 1898, Fairbanks was appointed a member of the United States and British Joint High Commission which met in Quebec City "for the adjustment of Canadian questions", including the Alaska boundary dispute.

[1] Fairbanks was elected vice president of the United States in 1904 on the Republican ticket with Theodore Roosevelt and served a four-year term, 1905 to 1909.

Roosevelt did not give Fairbanks a significant role in his administration, and (having chosen not to seek reelection) strongly promoted William Howard Taft as his potential successor in 1908.

When Charles Evans Hughes was nominated, Fairbanks was selected by the convention as the vice presidential nominee, which would have returned him to office under a different president, a feat previously accomplished only by George Clinton and John C. Calhoun.

In November, Hughes and Fairbanks lost a close election to the Democratic incumbents Woodrow Wilson and Thomas Marshall.