Fletcher joined Theodore Roosevelt's Rough Riders as a private in Troop K. He served in the U.S. Army, both in Cuba and in the Philippines for two years.
He entered the diplomatic service under President Roosevelt's administration as secondary secretary of the United States legation in Havana, Cuba. In 1903, he was transferred to Peiping and then, in 1905, as secretary to the legation in Lisbon, Portugal. In 1907, he returned to China and was negotiated an agreement whereby U.S. capital was allowed to participate on equal terms with European capital for the first time.
President Taft named him U.S. Minister to Chile in 1909. He was in that position until 1914, by which time the mission had been raised to the status of an Embassy, making him the first United States Ambassador to Chile. He served in that role until March 9, 1916.
In 1916, President Woodrow Wilson appointed him United States Ambassador to Mexico, his term coinciding with the height of World War I. He served as Ambassador in Mexico until January 25, 1919, after which point he returned to the United States.
In 1920, after directing the State Department's Latin American affairs for a year, he resigned and was appointed Under Secretary of State by President Warren G. Harding, serving from March 8, 1921 until March 6, 1922, under Secretary Charles Evans Hughes.
He served as Ambassador to Belgium from 1922 until 1924 under both Harding and his successor, Calvin Coolidge, who became President after Harding's death in 1923. In 1923, he was sent to the Pan-American Conference in Santiago, taking the place of Secretary of State Charles Evans Hughes who declined to go.
From April 2, 1924 until August 3, 1929, he was appointed by Coolidge and served as the Ambassador to Italy.
On April 22, 1930, President Hoover appointed him chairman of the United States Tariff Commission following the Tariff Act of 1930.
From 1934 to 1936, he was the Chairman of the Republican Party and was a delegate to the Republican national conventions in 1936 and 1940.