Named after his uncle, a Revolutionary War hero, he was born in Virginia, he came to Florida in 1814 as the personal aide to General Andrew Jackson. 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. 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 a victory at the battle of Wahoo Swamp. He was replaced as governor by President Martin Van Buren on December 2, 1839. During his 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.

During the 1830s, he constructed 2 plantations on land that he purchased in Leon County. Orchard Pond Plantation was located north of Tallahasee 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.