Founded in 1786, Knoxville is the third-largest city in the state of Tennessee, behind Memphis and Nashville, and is the county seat of Knox County.  It is also the largest city in East Tennessee, and the second-largest city (behind only Pittsburgh) within the region of Appalachia.

Knoxville is the principal city of the Knoxville Metropolitan Statistical Area with a metro population of 655,400.

Of Tennessee's four major cities, Knoxville is second oldest to Nashville, which was founded seven years earlier. After Tennessee's admission into the Union in 1796, Knoxville was the state's first capital, in which capacity it served until 1819, when the capital was moved to Murfreesboro, prior to Nashville receiving the designation.

The city was named in honor of the first Secretary of War, Henry Knox.

One of Knoxville's nicknames is The Marble City.  In the early 20th century, a number of quarries were active in the city, supplying Tennessee pink marble (actually Ordovician limestone of the Holston Formation) to much of the country. Notable buildings such as the National Gallery of Art in Washington are constructed of Knoxville marble. The National Gallery's fountains were turned by Candoro Marble Company, which once ran the largest marble lathes in the United States. Knoxville was once also known as the Underwear Capital of the World.  In the 1930s, no fewer than 20 textile and clothing mills operated in Knoxville, and the industry was the city's largest employer. In the 1950s, the mills began to close, causing an overall population loss of 10% by 1960.

Knoxville is also the home of the University of Tennessee's flagship campus. The university's sports teams, called the "Volunteers" or "Vols", are extremely popular in the surrounding area. In recognition of this popularity, the telephone area code for Knox County and eight adjacent counties is 865 (VOL).

Knoxville is also the home of the Women's Basketball Hall of Fame, almost entirely thanks to the popularity of Pat Summitt and the University of Tennessee women's basketball team.

McGhee Tyson Airport serves Knoxville and the Tennessee Air National Guard.