At the time of European encounter, the inhabitants of the area that became Guilford County were a Siouan-speaking people called the Cheraw.

[8] Friedens Church, whose name means "peace" in German, is in eastern Guilford County, at 6001 NC Hwy 61 North, northwest of Gibsonville.

[10] On March 15, 1781, during the American Revolution (1775–1783), for independence from Great Britain, the Battle of Guilford Court House was fought just north of present-day Greensboro between Generals Charles Cornwallis and Nathanael Greene.

His decision ultimately led him to take his army north into Virginia, leading eventually to his defeat and surrender later in October 1781 at Yorktown, Virginia, after a long siege, by a combined force of American and French Royal troops and blockading French Navy warships on the Chesapeake Bay.

[citation needed] In 1808, the town of Greensboro replaced the hamlet of Guilford Court House as the county seat.

[11] In the antebellum era, many of the county's residents were opposed to slavery, including Lutherans, Quakers and Methodists.

The county was a stop on the Underground Railroad, for which volunteers aided refugee slaves en route to freedom in the North.

Guilford College was founded in 1837 as the New Garden Boarding School; its name was changed in 1888 when the academic program was expanded considerably.

Greensboro College, established by the Methodist Church through a charter secured in 1838, was one of the earliest institutions of higher education for women in the United States.

It was the nation's second college established under the federal Morrill Act of 1890 and was the first state-supported school for people of color in North Carolina.

In 1963, the university was changed to a coed institution, and its curriculum was gradually expanded to include graduate work.

[16] Immanuel Lutheran College and Seminary was located on a small campus on East Market Street from 1905 until it closed in 1961.

When the school moved to the county seat of Greensboro, Lutherans built a large granite main building for it.

[19][20] In 1960 North Carolina still operated by racial segregation laws, and maintained the disenfranchisement of most black voters established at the end of the 19th century to suppress the Republican Party.

Following World War II, African-American veterans and young people heightened their activities in the American civil rights movement.

Guilford County was the site of an influential protest in 1960 when four black students from the North Carolina A&T State University in Greensboro started an early sit-in.

In this incident the predominantly African American Communist Workers Party (CWP) led a march protesting the Ku Klux Klan and other white-supremacist groups through a black neighborhood in southeastern Greensboro.

In 1980 the case attracted renewed national attention when the six shooter defendants were found "not guilty" by an all-white jury.

In 1985 families and friends of the victims won a civil case for damages against the city police department and other officials for failure to protect the African Americans; monies were paid to the Greensboro Justice Center.

The county is governed by a Board of Commissioners, containing a representative for each of nine districts, with each member serving a four-year term.

It provides primary law enforcement services for the unincorporated areas of Guilford County and to municipalities that have not established their own police departments.

The Sheriff's Office supplements the Greensboro and High Point city police departments, having full jurisdiction and ability to provide law enforcement services within both municipalities.

The Sheriff's Office maintains detention centers in both Greensboro and High Point, and provides security to the state courthouses in both cities.