Before European colonizers arrived in the region, Knoxville was home to Native American peoples. Native Americans settled in the area during the Woodland period between 1000 B.C. to A.D. 1000. Archaeologists unearthed a burial mound constructed around 1000 – 1400 A.D. in the area, and the University of Tennessee developed around this structure. The Cherokee peoples became the dominant tribe in the area during the 18th century. This tribe was consistently at war with the Creek and Shawnee peoples at the time. The Cherokee people called the modern-day Knoxville area kuwanda'talun'yi, which means "Mulberry Place." The first Europeans discovered the region during the late 17th century. The first significant excursion in the area was the Timberlake Expedition in late 1761. However, tensions increased between the Cherokee people and European colonizers during the late 1700s as more and more Europeans settled there. These settlers created the Holston Treaty between themselves and the Cherokee people, but issues arose. There was a dispute about the land agreed upon, and when negotiations took place in 1793, some Knoxville colonizers decided to attack the Cherokee people and killed the chief's wife. Peace was eventually restored in 1794. The city became a regional merchandising center due to its location, which lies at the confluence of three major rivers in the Tennessee Valley, which led to steamboats passing by the town. The East Tennessee and Georgia Railroad reached the city in 1855, leading to a population boom that doubled in size. The American Civil war threatened and negatively affected the city, prompting northern investors to help rebuild the city. The town became a significant center of textiles, food, and iron products after these investors created 97 factories between 1880 and 1887. This economic boom drove a new developmental and population boom in the city. The city's population then expanded from 5,000 people in 1860 to over 32,000 by 1900. The Great Depression affected the city, as its economy heavily relied on manufacturing. The valley in which the town lies was also prone to flooding, meaning that large areas of farmlands were spoiled due to soil erosion. Townsfolk established the Tennessee Valley Authority (TVA) in 1933, which built a series of hydroelectric and other power plants to combat this flooding and erosion. The city has recently focused on bringing life back to the downtown area. Knoxville's downtown area is now home to the Women's Basketball Hall of Fame, the Knoxville Convention Center, the redevelopment of Market Square, a new visitor's center, a regional history museum, a Regal Cinemas theater, and trendy restaurants and bars.

The city of Knoxville, Tennessee, offers a range of activities and attractions, such as the following:

Ijams Nature Center: The park, which is 315 acres, proffers space to walk, cycle, picnic, paddle, and swim. The center also presents live animal exhibits and displays, markets, and has a wedding venue.
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Zoo Knoxville: This zoo is the living quarters for over 800 species of animals. It is the birthplace of the first and second African elephants in the U.S. and holds the record for the most births of red pandas. The East Zoo hosts Asian habitats and animals, marine animals, and birdlife. The West Zoo is home to African primates, giraffes, rhinos, elephants, and lions.

Knoxville Museum of Art: This museum proudly showcases the creativity of East Tennessee and has a permanent exhibit, Higher Ground, which honors the area's artists.