In 1828, George McGarrah settled at Big Spring with his family on the modern day corner of Spring and Willow, founding the town of Washington. The following year, Postmaster Larkin Newton changed the name to avoid confusion, as there was already a town called Washington in Hempstead County.

Two councilmen selected the name in honor of their previous hometown: Fayetteville, Tennessee, which was itself named for Fayetteville, North Carolina. That original Fayetteville was named for General Lafayette, a French general who helped the colonies gain independence in the American Revolutionary War.

The town was founded on land that had previously been set aside for the western Cherokee Nation. Before the Cherokees, the land had been hunted by the Osage and Quapaw tribes.

In 1836, Lodowic Brodie and A.B. Anthony built the city's first brick building--a school on what is now called School Avenue, between Meadow and Center.

In the Battle of Pea Ridge (March 7-8, 1862), Federal forces led by Brig. Gen. Samuel R. Curtis moved south from central Missouri, driving Confederate forces into northwestern Arkansas. The Confederate counter-offensive launched by Maj. Gen. Earl Van Dorn was one of the few in which a Confederate army outnumbered its opponent, but Curtis held off the Confederate attack on the first day and drove Van Dorn's force off the battlefield on the second, establishing Federal control of most of Missouri and northern Arkansas.

Bill and Hillary Clinton's first home was in Fayetteville, where they both taught at the University of Arkansas School of Law. The house where they were married and lived is now the Clinton House Museum, featuring campaign memorabilia, a replica of Hillary's wedding dress, a photo gallery, and footage from Bill's early campaign commercials.

The University of Arkansas student body voted to change the name of the school mascot (originally the Cardinals) in 1910 to the Arkansas Razorbacks after a hard-fought battle against LSU in which they were said to play like a "wild band of Razorback hogs" by former coach Hugo Bezdek.

Bikes Blues and BBQ (BBBQ) has taken place annually on Dickson Street since its inception in 2000. The motorcycle rally gives up to $0.65 per attendee to local charities, making it the largest charity motorcycle rally in the world with upwards of 250,000 participants.

The city is on the outskirts of the Boston Mountains, which form the highest portion of the Ozarks.

Although not one of Arkansas' original state highways, the path that AR 265 follows is one of the state's oldest. Originally a Native American trace named the Great Osage Trail, the route was used as a Military Road from St. Louis to Fort Smith, and later as the Trail of Tears, when thousands of Native Americans were forcibly removed from their ancestral homelands.