As an unincorporated community, Bethesda has no official boundaries. The United States Census Bureau defines a census-designated place named Bethesda whose center is located at . The United States Geological Survey has defined Bethesda as an area whose center is at , slightly different from the Census Bureau's definition. Other definitions are used by the Bethesda Urban Planning District, the United States Postal Service (which defines Bethesda to comprise the zip codes 20810, 20811, 20813, 20814, 20815, 20816, and 20817), and other organizations. According to estimates released by the U.S. Census Bureau in 2013, the community had a total population of 63,374. Most of Bethesda's residents are in Maryland Legislative District 16.
Bethesda is situated along a major thoroughfare that was originally the route of an ancient Native American trail. Henry Fleet (1602-1661), an English fur trader, was the first European to travel to the area, which he reached by sailing up the Potomac River. After staying for several years (1623–27) with the Piscataway tribe — variously as a guest or prisoner — he returned to England, spoke of potential riches in fur and gold, and won funding for another North American expedition.
Most early settlers in Maryland were tenant farmers who paid their rent in tobacco. The extractive nature of tobacco farming meant that colonists continued to push farther north in search of fertile land, and in 1694 Henry Darnall (1645–1711) surveyed a 710-acre area that became the first land grant in present-day Bethesda. Rural tobacco farming was the primary way of life in Bethesda throughout the 1700s; while the establishment of Washington, D.C. in 1790 deprived Montgomery County of Georgetown, its economic center, the event had little effect on the small farmers throughout Bethesda.
Between 1805 and 1821, the area of present-day Bethesda became a rural way station after development of a toll road, the Washington and Rockville Turnpike, which carried tobacco and other products between Georgetown and Rockville, and north to Frederick. A small settlement grew around a store and tollhouse along the turnpike. By 1862, the community was known as "Darcy's Store" after the owner of a local establishment, William E. Darcy. The settlement was renamed in 1871 by the new postmaster, Robert Franck, after the Bethesda Meeting House, a Presbyterian church built in 1820 on the present site of the Cemetery of the Bethesda Meeting House. The church burned in 1849 and was rebuilt the same year about 100 yards south at its present site.