Partly due to his inability to share in the amusements of his fellows as a result of a deformity due to a vaccine poisoning suffered before he was five (the poison permanently arresting the growth and development of his legs), Legaré was an eager student and was president of the Clariosophic Society at the College of South Carolina (now University of South Carolina at Columbia), from which he graduated in 1814 with the highest rank in his class and with a reputation for scholarship and eloquence.
After graduation he studied the law for three years, did advanced work in Paris and Edinburgh in 1818 and 1819 and in 1822 was admitted to the South Carolina Barometer He also founded and edited the Southern Review between 1828 and 1832. From 1830 until 1832 he was the attorney general of South Carolina, and he supported states" rights, he strongly opposed nullification.
He was Attorney General until he was appointed chargé d"affaires to Brussels in 1832, serving there until 1836.
On his return he was elected to the 25th Congress as a Democrat, but failed in a re-election bid the following term. In 1841 President John Tyler named him Attorney General of the United States and he served in that office until his death.
He also served as Secretary of State ad interim from May 8, 1843, until his death. He died in Boston while attending ceremonies for the unveiling of the Bunker Hill Monument.
He was first interred in Mount Auburn Cemetery in Cambridge, Massachusetts, and was later re-interred in Magnolia Cemetery in Charleston.
The USCGC Legare, which is a medium endurance cutter, was named in his honor.
After practicing for a time in Charleston, he became a member of the South Carolina House of Representatives, serving between 1820 and 1821 and then again between 1824 and 1830.