Following his admission to the New York Bar, MacMurray sought a career in government.
A letter of commendation from Woodrow Wilson helped MacMurray secure an opportunity to take the foreign service examination.
In 1907, he was appointed as Consul-General and Secretary of Legation in Bangkok, Siam, and then became second secretary at the U.S. embassy in St. Petersburg.
There he worked under ambassador William Woodville Rockhill, who was credited with helping to shape the United States' open door policy towards China.

Upon returning to Washington in 1911, MacMurray was made chief of the Division of Near Eastern Affairs, a position he held until 1913.
He then had several appointments in East Asia: from 1913 to 1917, he was secretary of Legation in Peking, China, and from 1917 to 1919, he was counselor of the embassy in Tokyo.
He had been offered a post as Minister to Siam in 1913, but declined in order to pursue the position in Peking.
He again returned to the State Department in 1919 to serve as Chief of Division for Far Eastern Affairs from 1919 to 1924.
During that time, MacMurray was involved as an observer to negotiations between China and Japan concerning the status of the Shandong Peninsula, and authored a book titled Treaties and Agreements with and Concerning China.
The book was a compilation of all treaties and agreements with China from 1894 to 1919, and was published by the Carnegie Endowment for International Peace.

MacMurray briefly served as Assistant Secretary of State from 1924 to 1925.
In 1925, he was appointed Minister to China under President Calvin Coolidge, who described him as "our top China expert".
He assumed the post in July 1925.
MacMurray was well regarded within the diplomatic community in Peking; Sir Ronald Macleay with the British delegation described him as friendly and agreeable, and relatively unburdened by the preconceived ideas and sentimentality towards China that afflicted several of his predecessors.
Macleay noted that MacMurray could express himself well and forcefully in diplomatic meetings, but that he was "rather academic", and may have lacked confidence in himself. "
I imagine that he allows himself very little freedom of action and refers to Washington on every possible occasion," wrote Macleay.
Another British diplomat, Sir Miles W. Lampson, recorded MacMurray's complaints that Washington allowed him little initiative, and seldom adopted his proposals.

Soon after arriving in China, MacMurray fell into disagreement with Washington over U.S. policy towards the ruling Kuomintang (Nationalist) government, which had been demanding immediate revisions to or a cessation of the treaty system in place between the two countries.
Whereas Washington wished to make concessions to the Nationalist government, MacMurray favored the enforcement of existing treaties.
These differences of opinion led him to resign in November 1929, whereupon he became a professor of International Relations at Johns Hopkins University.

In 1933, MacMurray returned to the foreign service.
On September 9 of that year, he was appointed Envoy Extraordinary and Minister Plenipotentiary to Estonia, Latvia and Lithuania—a position he held until 1936.
From 1936 to 1941, MacMurray served as Ambassador Extraordinary and Plenipotentiary in Turkey.
He returned to Washington in 1942 and worked as a special assistant to the Secretary of State until his retirement in 1944.
Following his admission to the New York Bar, MacMurray sought a career in government. A letter of commendation from Woodrow Wilson helped MacMurray secure an opportunity to take the foreign service examination. In 1907, he was appointed as Consul-General and Secretary of Legation in Bangkok, Siam, and then became second secretary at the U.S. embassy in St. Petersburg. There he worked under ambassador William Woodville Rockhill, who was credited with helping to shape the United States' open door policy towards China.
Upon returning to Washington in 1911, MacMurray was made chief of the Division of Near Eastern Affairs, a position he held until 1913. He then had several appointments in East Asia: from 1913 to 1917, he was secretary of Legation in Peking, China, and from 1917 to 1919, he was counselor of the embassy in Tokyo. He had been offered a post as Minister to Siam in 1913, but declined in order to pursue the position in Peking. He again returned to the State Department in 1919 to serve as Chief of Division for Far Eastern Affairs from 1919 to 1924. During that time, MacMurray was involved as an observer to negotiations between China and Japan concerning the status of the Shandong Peninsula, and authored a book titled Treaties and Agreements with and Concerning China. The book was a compilation of all treaties and agreements with China from 1894 to 1919, and was published by the Carnegie Endowment for International Peace.
MacMurray briefly served as Assistant Secretary of State from 1924 to 1925. In 1925, he was appointed Minister to China under President Calvin Coolidge, who described him as "our top China expert". He assumed the post in July 1925. MacMurray was well regarded within the diplomatic community in Peking; Sir Ronald Macleay with the British delegation described him as friendly and agreeable, and relatively unburdened by the preconceived ideas and sentimentality towards China that afflicted several of his predecessors. Macleay noted that MacMurray could express himself well and forcefully in diplomatic meetings, but that he was "rather academic", and may have lacked confidence in himself. "I imagine that he allows himself very little freedom of action and refers to Washington on every possible occasion," wrote Macleay. Another British diplomat, Sir Miles W. Lampson, recorded MacMurray's complaints that Washington allowed him little initiative, and seldom adopted his proposals.
Soon after arriving in China, MacMurray fell into disagreement with Washington over U.S. policy towards the ruling Kuomintang (Nationalist) government, which had been demanding immediate revisions to or a cessation of the treaty system in place between the two countries. Whereas Washington wished to make concessions to the Nationalist government, MacMurray favored the enforcement of existing treaties. These differences of opinion led him to resign in November 1929, whereupon he became a professor of International Relations at Johns Hopkins University.
In 1933, MacMurray returned to the foreign service. On September 9 of that year, he was appointed Envoy Extraordinary and Minister Plenipotentiary to Estonia, Latvia and Lithuania—a position he held until 1936. From 1936 to 1941, MacMurray served as Ambassador Extraordinary and Plenipotentiary in Turkey. He returned to Washington in 1942 and worked as a special assistant to the Secretary of State until his retirement in 1944.
John Van Antwerp MacMurray