Greenough studied in Rome from 1826; he became influenced by Bertel Thorvaldsen whom he greatly admired.
In 1832, he received an order from the Congress of the United States for a large statue of George Washington for the Capitol Rotund. When completed, this work caused much controversy: the classical style did not conform with American taste. The statue was displayed in various localities - today it can be seen at the National Museum of American History, Smithsonian Institution, Washington D.C.
In 1851 he returned to Washington to superintend its erection, and in the autumn of 1852 he was attacked by brain fever, of which he died in Somerville near Boston on the 18th of December.
Among other works of Greenough may be mentioned a bust of Lafayette, the Medora and the Venus Victrix in the gallery of the Boston Athenaeum.
Greenough was a man of wide culture, and wrote well both in prose and verse.