East Tennessee is a name given to approximately the eastern third of the state of Tennessee. Unlike the names given to regions or portions of many of the American states, the term East Tennessee can be precisely defined. It is the portion of the state located within the Eastern Time Zone and Marion County, located within the Central Time Zone. East Tennessee is noted for its mountains, particularly the Great Smoky Mountains portion of the Blue Ridge Mountains, but in fact has many and varied landforms.

The major cities of East Tennessee are Knoxville and Chattanooga. Other important cities include the "Tri-Cities" of Kingsport, Johnson City, and Bristol, located in the extreme northeasternmost part of the state, an area previously and traditionally referred to as Upper East Tennessee, although today the term Northeast Tennessee is preferred.

East Tennessee is noted for the presence of many institutions of higher learning, perhaps most notably the Knoxville and Chattanooga campuses of the University of Tennessee and East Tennessee State University in Johnson City. Knoxville and Chattanooga also contain major operations of the Tennessee Valley Authority. The U.S. nuclear weapons program was largely developed during World War II at Oak Ridge. Kingsport is the home of Tennessee's largest single industial employer in Eastman Chemical Company, formerly the chemical division of Kodak, and the Aluminum Company of America, now Alcoa, initially attracted to the area by its potential for low-cost hydroelectric development, still maintains a major operation in its namesake town of Alcoa, just south of Knoxville.

East Tennessee is the only part of the state which has consistently voted Republican since Reconstruction. The region was the only area of the state to oppose secession before the Civil War, and as a result became an early base for the then-new Republican Party. This allegiance has continued to this day. The state's 1st and 2nd Congressional Districts, based in the Tri-Cities and Knoxville respectively, are considered to be so heavily Republican that Republican nomination is tantamount to a general election victory. In contrast, the Democratic primary was the real contest in Middle and West Tennessee until the mid-1960s. Despite the Republican majorty, there are signifigant Democratic Party enclaves in several heavily populated areas: Hamilton County, Knox County and Washington County

Unlike the geographic designations of regions of most U.S. states, the term East Tennessee has legal as well as socioeconomic meaning. East Tennessee, along with Middle Tennessee and West Tennessee, comprises one of the state's three Grand Divisions. According to the state constitution, no more than two of the state supreme court's five justices can come from any one Grand Division. A similar rule applies to certain other commissions and boards as well, to prevent them from showing a geographic bias.