The land on which Sykesville sits started out as part of the 3,000-acre (12 km²) Springfield Estate, owned by wealthy Baltimore shipbuilder William Patterson. In 1803, Patterson’s daughter Elizabeth Patterson married Napoléon Bonaparte’ brother Jérôme, but when she arrived in Europe as Jérôme’s bride, Napoléon refused to let Betsy Patterson Bonaparte set foot on land. Napoléon refused the marriage of the two, and would not let Elizabeth set foot on France’s soil. He was determined that Jérôme marry into royalty, and sent Betsy back home. Denied by Napoléon, she was never able to see her husband again, leaving her to raise their son alone in the United States. Upon the death of William in 1824, his son George Patterson inherited the estate.
In 1825, George Patterson sold 1,000 acres (4.0 km² 1.6 sq mi) of Springfield Estate to his friend and business associate,James Sykes.
A tract of land on the Howard County side of the Patapsco Rivercontained an old saw and grist mill. In 1830 Sykes replaced it with a newer mill and constructed a five-story stone hotel, to take care of railroad personnel and the tourist trade. In 1831 the Baltimore and Ohio Railroad (B&O) extended its main line to “Horse Train Stop”, since Sykesville had yet to be named. Other businesses moved into the area, including two general stores, new mills, churches and a post office.
In 1832 the town managed to gain control of a barn across the Patapsco River, the dividing line between Carroll and Howard County, but the citizens were forced to return the barn under threat of federal troops.
Much of the town was destroyed by a flood in 1868. The town was rebuilt on the Carroll County side of the river.
The town was incorporated in 1904. A weekly newspaper, the Sykesville Herald, was founded in 1913 and published regularly until the 1980s.