He was born in Corsica, Pennsylvania.
He was appointed to the United States Naval Academy on 30 July 1864. Graduating tenth in the class of 1868, Thompson first went to sea in Contocook in the West Indian Squadron. He later served in Franklin, Richmond, and Guard of the Mediterranean Squadron; as well as in Wachusett and at the Naval Torpedo Station, Newport, Rhode Island.
Commissioned ensign on 19 April 1869, and promoted to master on 12 July 1870, he resigned from the Navy on 18 November 1871, to study law in his brother's office. After he was admitted to the Pennsylvania Bar in 1872, he was still not satisfied with his legal training so he studied law at Harvard and graduated from that school in 1874. Thompson subsequently practiced law in Boston and was a member of the Boston Common Council from 1876 to 1878. He later became interested in mining and smelting enterprises.
He was an organizer of the Navy Athletic Association and the donor of the Thompson Cup, which is awarded to the midshipman who contributes most to the advancement of athletics at the Naval Academy. He also helped to organize the New York Chapter of the United States Naval Academy Alumni Association and served as its first president and as a trustee of the Naval Academy Alumni Association at Annapolis, Maryland.
Thompson was president of the Society of Naval Architects and Marine Engineers and president of the Navy League. He also visited Japan at the invitation of the Japanese government and was awarded the Order of the Rising Sun, Second Class, by the Emperor. He also received the Order of Vasa by the government of Sweden, and the Cross of Commander, French Legion of Honor, by the French government.
Robert Means Thompson died in Fort Ticonderoga, New York.
The United States Navy destroyer USS Thompson (DD-627) was named in his honor.