[7] The Trading Path (later called the "Unicoi Turnpike") passed by the future site of Murphy, connecting the Cherokee lands east of the mountains with what were known to European colonists as the "Overhill Towns" of Tennessee.

[10] European Americans later renamed the settlement as Murphy for North Carolina politician Archibald Murphey.

[9] The original spelling of the town was to be "Murphey" but a clerk or stenographer of the North Carolina General Assembly misspelled the name and “Murphy” stuck.

[11][12] In 1836, during the Cherokee removal known as the Trail of Tears, the United States army built Fort Butler in what is today Murphy.

From Fort Butler, the Cherokee were taken over the mountains on the Unicoi Turnpike to the main internment camps at Fort Cass (today Charleston, Tennessee), prior to their forcible removal to territory west of the Mississippi River, in what became known as Indian Territory (today's Oklahoma).

There are no visible remains of Fort Butler, but the site can be visited and historical markers provide facts and interpretation about its history.

In addition, the Cherokee County Historical Museum, located in Murphy, provides information about the Trail of Tears.

Today the track and right-of-way are still in place, owned by the North Carolina Department of Transportation, but the line is inoperable.

[17] Architect James Baldwin designed the Cherokee County Courthouse, located in downtown Murphy, in a Beaux-Arts style.

It is listed on the National Register of Historic Places, along with Harshaw Chapel and the Robert Lafayette Cooper House.

The building later housed the town police department until 2024 and has been occupied by the Cherokee County Historical Museum since its start in 1977.

[27] In 1945, Paul Westmoreland wrote his song “Detour (There's a Muddy Road Ahead)" while traveling to Murphy.

The hospital was a two-story white brick building atop a hill on Peachtree Street downtown.

[30] The 22-bed Murphy General Hospital was built by Dr. F. V. Taylor in 1941 and closed in July 1969 due to insufficient staff and property.

[23][31] In January 1974 the Murphy Town Council approved spending $4,000 on a study to see whether constructing a new hospital was feasible.

Following this study, Providence Hospital closed in 1978, and Murphy Medical Center was founded in nearby Peachtree in 1979.

[33] In approximately 1961, the two-mile, four lane Dr. William A. Hoover Bridge was built over the Hiwassee River near Murphy to serve US Route 19.

[44] On May 31, 2003 Olympic Park bomber Eric Rudolph was captured behind a Murphy Save-A-Lot by rookie police officer Jeff Postell.

[45] In October 2024, one of the oldest remaining buildings in downtown Murphy, the Akin-Axley-Davidson house at 69 Valley River Avenue, was demolished.

[56] Harrah's Cherokee Valley River, a tribal casino that opened in Murphy in 2015, is also a major job supplier.

[57] Additionally, there are two Bitcoin mining operations in Murphy – one by Core Scientific[58] and the other by Atlas Technology Group.

One of the farms, called Martins Creek Solar Project, alone provides "enough electricity to power more than 150 average-sized homes and enough revenue for the district to staff approximately two full-time teachers.

WKRK 1320 AM, WCVP 600 AM, and WCNG 102.7 FM are three radio stations currently broadcast from Murphy.

[83] Murphy and all of Cherokee County are served by Erlanger Western Carolina Hospital, certified by the United States Department of Health and Human Services.

The department had for decades been located in the basement of the old Carnegie Library at 93 Peachtree Street next to the courthouse.

[5] Murphy is located in southwestern North Carolina, approximately halfway between Atlanta, Georgia and Knoxville, Tennessee.

[89] The location in the Blue Ridge Mountains has helped the community retain a fairly rural character, surrounded by wildlife such as bear, deer, fox and recently reintroduced elk.

[90] Murphy has a humid subtropical climate, (Cfa) according to the Köppen classification, with hot, humid summers and cool to mild winters,[91] with low temperatures significantly cooler than other parts of the Southeast, due in part to the elevation.

Like the rest of the southeastern U.S., Murphy receives abundant rainfall, greatest in winter and enhanced by the elevation.

[92] Blizzards are rare but possible; the 1993 Storm of the Century dropped 15 inches (38 cm) in 24 hours with more snowfall continuing up to 38" in some areas, causing widespread power outages and natural disasters.