As chairman of the Tioga County Republican Party in the late 1860s, Platt met Senator Roscoe Conkling, boss of upstate New York Republicans.  Under Conkling's tutelage, Platt was elected two years later to the first of two consecutive terms in Congress (1873-1877), and became a trusted lieutenant in Conkling's political machine.  In January 1881, Conkling orchestrated Platt's election to the U.S. Senate by the New York State Legislature.  Once in Washington, the two men quickly became embroiled with James Garfield, the new Republican president, over control of patronage at the New York City Port.  On May 16, 1881, to nearly everyone's surprise, New York's two senators resigned, hoping to be vindicated with reelection by the state legislature.  In early June, members of another Republican faction blackmailed Platt into withdrawing after they discovered him in bed with a woman who was not his wife.  A few weeks later, the state legislature elected two new senators.

Conkling retired from politics, but Platt returned to Owego, where he worked over the next few years building his own political machine, modeled after Tammany Hall, the Democratic machine in New York City.  Unlike many political bosses, however, he did not manipulate his power to gain personal wealth, nor rule with a heavy hand; in fact, his soft touch earned him the nickname, "the Easy Boss."  During the 1880s, he served as president of the United States Express Company, and built important friendships with major businessmen, who looked to him to help ease government regulations.  He also served as president of the New York State Quarantine Board and as a member of the National Republican Committee.

Platt moved to Manhattan where he enhanced his control over New York's Republican Party.  In the 1894 elections, Republicans captured the governorship (under Levi Morton) and both houses of the legislature, which two years later elected Platt to the first of two terms in the U.S. Senate (1897-1909).  He was largely uninterested in national policy or politics, though, and initiated no important legislation, seldom spoke on the Senate floor, and failed to earn the respect of his colleagues.  However, he continued to be deeply involved in state politics, returning every weekend to Manhattan, where he met with state or local politicians on Sundays at the Fifth Avenue Hotel.  The meetings became known as "Platt's Sunday School" or the "Amen Corner" because his subordinates were said to always agree with him.  

In 1898, the Republican Party in New York faced an uphill battle in the upcoming elections, so Platt reluctantly backed reformer Theodore Roosevelt for governor.  The senator's concerns proved accurate when Governor Roosevelt refused to appoint Platt's men to patronage positions and endorsed regulatory legislation that angered the Easy Boss's business cronies.  In order to get Roosevelt out of New York, Platt successfully worked to win the governor the Republican vice presidential nomination in 1900.  Ironically, Roosevelt became president after the death of President William McKinley in September 1901.  Furthermore, although the new governor of New York, Benjamin Odell, was a Platt protégé, he maneuvered control of the state Republican Party away from his former mentor.  After retiring in 1909, Platt lived quietly at his Fifth Avenue Hotel suite in Manhattan, where he died the next year.