Political Career in New York
On July 15, 1908, Copeland married Frances Spalding. The same year, Copeland moved to New York City to take a position as dean at the New York Homeopathic Medical College and Flower Hospital, a position he left in 1918 to serve as President of the New York Board of Health. He gained much positive public attention for keeping New Yorkers calm during the influenza outbreak of 1918.
In 1922, Copeland ran as a Democrat for the U.S. Senate, defeating first-term Republican Senator William M. Calder. Franklin D. Roosevelt served as his honorary campaign manager for this election. Copeland was re-elected in 1928 over Republican challenger Alanson B. Houghton, the U.S. Ambassador to Britain and a former U.S. Representative. Copeland was again re-elected in 1934, this time defeating future U.S. Congressman E. Harold Cluett.
During his three terms in the Senate, Copeland served as chairman of the U.S. Senate Committee on Rules and Administration from 1933 to 1936 and chairman of the Committee on Commerce from 1935 to 1938. In 1935-1936 Copeland served as Chairman of the highly controversial Copeland Committee, which gave a scathing review of air traffic safety and the operation of the Bureau of Air Commerce. Copeland served as primary author and sponsor of the Federal Food, Drug, and Cosmetic Act of 1938, an important consumers right law. He was the primary sponsor of the Copeland "Anti-kickback" Act, which targeted kickbacks to federal contractors, subcontractors and officials from construction employees.
Copeland was close to the regular Democratic organization in New York, the boss-led Tammany Hall. He was a conservative Democrat and not especially supportive of his fellow New Yorker, President Franklin Roosevelt's New Deal policies. He was also a friend of Harry S. Truman when they both served in the U.S. Senate. Copeland was known for his successful efforts to bring air conditioning to the Senate.
In 1937 he lost the Democratic nomination for Mayor of New York City to Judge Jeremiah T. Mahoney, and the Republican nomination to incumbent Republican Mayor Fiorello H. LaGuardia. Senator Copeland died in office on June 17, 1938 and was buried at Mahwah Cemetery in Mahwah, New Jersey.
| Office | Type | Location | Party | Elected | Took Office | Left Office |
| Mayor of Ann Arbor, Michigan | Executive | Ann Arbor, Michigan | Republican | 1900 | March 4, 1901 | March 4, 1903 |
| U.S. Senator (Class 1) from New York | Legislature | Washington, DC | Democrat | 1922 | March 4, 1923 | March 4, 1929 |
| U.S. Senator (Class 1) from New York | Legislature | Washington, DC | Democrat | 1928 | March 4, 1929 | March 4, 1935 |
| U.S. Senator (Class 1) from New York | Legislature | Washington, DC | Democrat | 1934 | March 4, 1935 | June 17, 1938 |
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