The first land patents in the Rockville area were obtained by Arthur Nelson between 1717 and 1735. Within three decades, the first permanent buildings in what would become the center of Rockville were established on this land. Still a part of Prince George's County at this time, the growth of Daniel Dulaney's Frederick Town prompted the separation of the western portion of the county, including Rockville, into Frederick County in 1748.

During Revolutionary times Rockville was known as Hungerford's Tavern the name of its most familiar landmark. At other times Rockville was known as Owen's Ordinary and Daley's Tavern. Owen's Ordinary was a small rest stop on Rock Creek Main Road (later the Rockville Pike), which stretched from George Town to Frederick Town.

On September 6, 1776, the Maryland Constitutional Convention agreed to a proposal introduced by Dr. Thomas Sprigg Wootton wherein Frederick County, the largest and most populous county in Maryland, would be divided into three smaller units. The southern portion of the county, of which Rockville was a part, was named Montgomery County. The most populous and prosperous urban center in this new county was George Town, but its location at the far southern edge rendered it worthless as a seat of local government. Rockville, a small, but centrally located and well travelled town, was chosen as the seat of the county's government. Thereafter, the village was referred to by all as Montgomery Court House. In the 1780s, the community was known as Williamsburg, the last of its names before its designation as Rockville.

In 1801, the Maryland General Assembly changed the name of the town to Rockville because of its location close to Rock Creek. Rockville remained small during the first two-thirds of the 19th century. The population grew from 200 in 1800 to 400 in 1846. Rockville became incorporated in 1860 and was governed by three commissioners until 1888, when the city's 400 residents elected the first Mayor and Council.

The first big change in the town's status began in 1873. The metropolitan branch of the Baltimore and Ohio Railroad came to Rockville, and frequent trains started going to and from Washington and the brand new B & O station each day. In July 1891, the Tennallytown and Rockville Railway inaugurated Rockville's first trolley service connecting to the Georgetown and Tennallytown Railway terminus at Western Avenue and Wisconsin Avenue. This provided service from Georgetown to Rockville, connecting Rockville to Washington, D.C. by trolley. Trolley service operated for four decades, until, eclipsed by the growing popularity of the automobile, service was halted in August 1935.

According to the United States Census Bureau, the city has a total area of 13.4 square miles (34.8 km²), with no major bodies of water. From a population of 6,934 in 1950, Rockville grew to a population of nearly 45,000 by 1980. According to the 2006 census update the population of Rockville had grown to 59,114.

Rockville has a four-member City Council, whose members, along with the Mayor, serve as the legislative body of the city. The largest employer of Rockville residents is the federal government. Rockville has one sister city: Pinneberg (Schleswig-Holstein, Germany).

The grave site of F. Scott Fitzgerald is located at St. Mary's Church, in the center of Rockville. The alternative rock band R.E.M. wrote and performed a song about Rockville, called "(Don't Go Back to) Rockville," that appears on the album Reckoning.