The first inhabitants of the Towson region were the Susquehannough people who hunted in the area. Though their region included all of Baltimore County, their primary settlement was along the mouth of the Susquehanna River.

Towson was settled in 1752 when two Pennsylvania brothers, William and Thomas Towson, began farming northeast of present-day York and Joppa Roads. William's son, Ezekial, started the Towson Hotel at York and Joppa Roads in 1768 to serve the increasing traffic of farmers bringing their produce and livestock to the port of Baltimore. The village became known as "Towsontown". Today a shopping mall is situated at the intersection of York Road and Joppa Road known as the "Towson Town Center".

In 1790, Charles Ridgely completed the magnificent Hampton Mansion just north of Towsontown, the largest private house in America at the time. The Ridgelys lived there for six generations, until 1948. It is now preserved as the Hampton National Historic Site and open to the public.

On February 13, 1854, Towson became the county seat of Baltimore County by popular vote. The Court House, still in use, was designed by Dixon, Balbirnie and Dixon and completed within a year, constructed of limestone and marble donated by the Ridgely family, on land donated by Towson merchant Grafton Bosley. The Courthouse was subsequently enlarged in 1910 through designs for north and south wings by Baldwin and Pennington. Expansion in 1926 and 1958 created an H-shaped plan. The Baltimore County Jail was built in 1855.

From 1850 to 1874, another notable land owner, Amos Matthews, had a farm of 150 acres (0.61 km) that — with the exception of the 17-acre (69,000 m) largely natural parcel where the Kelso Home for Girls (currently Towson YMCA), was later erected — was wholly developed into the neighborhoods of West Towson, Southland Hills and other subdivisions beginning in the middle 1920s.

The former Grafton Bosley estate 'Uplands', Towson MD. after becoming the Presbyterian Home of Maryland (photo abt 1930)

During the Civil War, Towson was the scene of two minor engagements. Many of Towson's citizens were sympathetic to the southern cause, so much so that Ady's Hotel, later the Towson Hotel and the current site of the Recher Theatre, flew a southern flag. The Union Army found it necessary to overtake the town by force on June 2, 1861. During the raid, the Union army seized weapons from citizens at Ady's Hotel. A local paper, in jest, referred to Towson as the “strongly fortified and almost impregnable city of Towsontown” and downplays the need for the attack, stating, “the distinguished Straw, with only two hundred and fifty men, has taken a whole city and nearly frightened two old women out of their wits.”

The second engagement took place around July 12, 1864 between Union and Confederate forces. On July 10, 1864, a 135-man Confederate cavalry detachment attacked the Northern Central Railway in nearby Cockeysville, under orders from Gen. Bradley T. Johnson. The First and Second Maryland Cavalry, led by Baltimore County native and pre-war member of the Towson Horse Guards, Maj. Harry W. Gilmor, attacked strategic targets throughout Baltimore and Harford counties, including cutting telegraph wires along Harford Road, capturing two trains and a Union General, and destroying a railroad bridge in Joppa, Maryland. Following what became known as Gilmor's Raid, the cavalry encamped in Towson overnight at Ady's Hotel where his men rested and Gilmor met with friends. The next day, a large federal cavalry unit was dispatched from Baltimore to overtake Gilmor's forces. Though outnumbered by more than two to one, the Confederate cavalry attacked the federal unit, breaking the federal unit and chasing them down York Road to around current day Woodbourne Avenue within Baltimore City limits. Gilmor's forces traveled south along York Road as far south as Govans, before heading west to rejoin Gen. Johnson's main force. Following the war, Gilmor served as the Baltimore City Police Commissioner in the 1870s.

The Towson fire of 1878 destroyed most of the 500 block along the York Turnpike causing an estimated $38,000 in damage.

During the summer of 1894, the Towson Water Company laid wooden pipes and installed fire hydrants that were connected to an artesian well near Aigburth Vale. On November 2, 1894, Towson was supplied with electric service through connection with the Mount Washington Electric Light and Power Company.

At the beginning of the century, Towson remained largely a rural community. Land continued to be sold by the acre, rather than as home parcels. Most residences lay within Towson proper: no houses existed west of Central Avenue along Allegheny or Pennsylvania avenues, and there were only three homes along the West Chesapeake Avenue corridor.

As the growth of Baltimore's suburbs became more pronounced after World War II, considerable office development took place in Towson's central core area. Many of the large Victorian and colonial-style residences in the vicinity of the Court House were demolished in the 1980s and 1990s for offices and parking.

Towson United Methodist Church

In 1839, Epsom Chapel became the first Christian house of worship in Towson, used by various denominations. As the population grew in the late 19th and early 20th centuries, several churches were built to serve the community, such as Calvary Baptist Church, Immaculate Conception Catholic Church, Trinity Episcopal Church, First Methodist Church, and Towson Presbyterian Church. Epsom Chapel was demolished in 1950 when Goucher College sold a portion of its property for development of the Towson Plaza shopping center, now Towson Town Center. First Methodist Church moved in 1958 to land also acquired from Goucher College and is now Towson United Methodist Church.