Named after his uncle, a Revolutionary War hero, he was born in Pittsfield, Prince George County, Virginia. In 1813 he left school to take part in the Creek War. He came favorably to the attention of General Andrew Jackson, and came to Florida in 1814 as his personal aide. He returned with General Jackson in 1821 to establish the territorial government after the United States acquired Florida from Spain in the Adams-Onís Treaty. In 1822, he decided to make Florida his home and opened a legal practice. In 1824 he married Mary Letitia Kirkman of Nashville at General Jackson's home, the Hermitage .
He was on the Legislative Council of the territory and served as a Delegate to the U.S. Congress. On March 16, 1836, he was appointed by President Andrew Jackson as the governor of the territory. During this first term, he led the Florida militia in fighting the Seminole Indians, winning victories at the second and third Battles of Wahoo Swamp. He was replaced as governor by President Martin Van Buren on December 2, 1839 following a dispute with Federal authorities over their assistance in the war. He crossed party lines to assist the presidential campaign of William Henry Harrison, who appointed him again as Governor. During this second term as governor, which began on March 19, 1841, he moved the territory closer to statehood and tried to minimize the financial problems that Florida experienced due to bank failures and a national business depression. He left office on August 11, 1844. In 1845 Florida became a State, and he again sought election as governor, but his role in the election of President Harrison adversely affected his campaign.
During the 1830s, he constructed two plantations on land that he purchased in Leon County. Orchard Pond Plantation was located north of Tallahassee and The Grove Plantation was located on Tallahassee's northern outskirts. Today it is on the National Register of Historic Places. The estate later became the home of Governor LeRoy Collins, and his wife Mary Call Collins, the great granddaughter of Richard Call. Richard Keith Call died at The Grove on September 14, 1862.
Call was the uncle of US Senator Wilkinson Call.
There are several streets in Florida named after Richard K. Call. Call Streets are in Tallahassee, Starke, Jacksonville, Hollywood, and High Springs.
In 1944, a United States Liberty ship named the SS Richard K. Call was launched.