With the assistance of former Governor Alexander Randall and others, he helped establish the "Madison Regency," a powerful dispenser of political patronage jobs to the Republican Party faithful.

"Boss" Keyes became known as a wily political manager, and saw the state Republican party through its evolution from an abolitionist-driven movement to its consolidation as a dominant and enduring force in Wisconsin.

In 1852 he was appointed to his first government position as a special agent of the post office by Postmaster General N. K. Hall under the administration of President Millard Fillmore.

Defeated at the Whig convention, he was invited to run for the local state assembly seat, but Keyes declined in the face of stronger Democratic opposition.

Though Keyes was involved in the formation of the Dane County Republicans, he also showed support for the anti-immigrant American "Know-Nothing" Party, being vice president of the Madison chapter.

[8] He rose through the ranks and formed alliances at party conventions, winning election as the Republican candidate for Dane County District Attorney in 1858.

At the Second Congressional District Republican Convention held that summer in La Crosse, Keyes led a group of young former Whigs of Dane County (including Wisconsin State Journal publishers Horace Rublee and David Atwood) to help secure the nomination of his friend Luther Hanchett for the U.S. Senate, despite Madison Republican Chauncey Abbott having been the presumed favorite.

Following Howe's victory, President Abraham Lincoln appointed Keyes Madison Postmaster, which granted him the power to reward Republican supporters with postal jobs, and punish enemies within the party.

A year later Randall was appointed by Lincoln as First Assistant Postmaster General, and with Keyes controlled jobs in more than a thousand post offices in the state.

He designated Keyes as a special agent of the post office, granting him free rail passes to visit all the postmasters in that district to instruct them to work towards Sawyer's election, which resulted in victory.

Randall warned him that "I want to stand fast by you so don't embarrass me or give your enemies a chance to go to the President and have me ordered to hurt [you] without anything from you to sustain me."

G. W. Heyer, the editor of the Wisconsin Daily Democrat, sought to persuade William H. Noland, a local African-American businessman, to run against Keyes as an independent.

Keyes passed on candidates Lucius Fairchild, Cadwallader C. Washburn and Rublee to support acclaimed Milwaukee lawyer Matthew H. Carpenter, who was duly elected senator by the legislature.

Never a wealthy man, Keyes' influence diminished with the rise of Republicans like lumber baron Sawyer and railroad lawyer Angus Cameron, who both would become U.S. senators without his assistance.

Despite Republicans winning a majority of the legislature in 1874, a bolt occurred when they voted for senator, resulting in Carpenter losing the seat to Cameron of La Crosse.

He considered it, but after Sen. Howe told him his exit would ensure Republican victories in the fall elections, Keyes decided to fight for his chairmanship at the next party convention.

When Blaine failed to win the nomination, Keyes successfully drove the party machine to give Wisconsin's electoral votes to nominee Rutherford B. Hayes.

Ironically, President Hayes' "Order Number 1" would crack down on federal patronage schemes and institute a merit system that would require an exam for a government job, as well as ban mandatory campaign donations from employees.

After a Republican state legislature was secured in November, Keyes was seen as the favorite over Howe and former senator Carpenter, as long as congressman Sawyer did not attempt a bolt with the Democrats.

Keyes next set his eyes on Sen. Angus Cameron's seat up in 1881, but his plans were foiled when Sawyer entered the contest and was elected in the state legislative caucus.

After Carpenter died a month later, the Wisconsin State Journal boomed Keyes to fill his seat, but Milwaukee Republicans rejected him in favor of the recently deposed Cameron.

Issuing an order banning state officers from federal positions, President Chester A. Arthur declined to reappoint Keyes postmaster.

He begged the party's "Old Guard" to persuade President William McKinley to appoint him to his old job as Madison postmaster, which was achieved on the recommendation of Sen. John C. Spooner.

Keyes married his second wife, Mrs. Louisa Sholes, in Dane County on December 4, 1866, and divorced her in 1882, retaining custody of their son Louis.