The crown jewel of this region is Great Smoky Mountains National Park, established as a national park in the 1930s. It is the most-visited national park in the Eastern United States. Much of the range is also protected as the Nantahala National Forest, and the Cherokee National Forest outside of the park.

The highest point in the Great Smokies is Clingmans Dome (6,642 feet, 2,030 meters), which is located within the Great Smoky Mountains National Park. A paved road leads to within 300 feet of the summit, and from there visitors can walk a trail to the top. A handicap-accessible tower is located at the summit, and on clear days visitors can see four states (Tennessee, North Carolina, South Carolina, and Georgia). Clingmans Dome is also the highest point in the State of Tennessee. The Smokies rise prominently above the surrounding low terrain. For example, Mount LeConte (6,593 feet, 2,010 meters) rises more than a mile above its base. Due to their prominence, the Smokies receive heavy annual amounts of precipitation. Over 80 inches of rain fall each year, and snowfall in the winter can be heavy, especially on the higher slopes.

The name of the area comes from the natural haze that often hangs over it. As in the neighboring Blue Ridge Mountains just to the east, hydrocarbons produced by trees and other local vegetation, as well as higher humidity produce a bluish cast to the sky, even over short distances. Visibility now is dramatically reduced by smog from both the Southeastern U.S. and the Midwest, and smog forecasts are prepared daily by the Environmental Protection Agency for both nearby Knoxville and Asheville.

Smog is also killing the spruce trees at higher elevations, while the invasive hemlock woolly adelgids attack the hemlocks, and the balsam woolly adelgids attack the firs. Japanese ladybird beetles have been brought in, in an attempt to control the adelgids.

Other subalpine species more typical of Maine and even Canada are also found at the highest elevations, above about 5000 feet or 1500 meters AMSL. Some bird migration actually takes place vertically, with the "local" birds going up and down the mountains rather than north and south.

Many wildflowers grow, including bee balm, fire pink, Solomon's seal, Dutchman's breeches, various Trilliums, and even hardy orchids like showy orchis.

There are two native species of rhododendron in the area. The Catawba rhododendron has purple flowers in May and June, while the rosebay rhododendron has shorter leaves and blooms a light pink in June and July. The orange-flowered and deciduous flame azalea closely follows along with the Catawbas. The closely-related mountain laurel blooms in between the two, and all of the blooms progress from lower to higher elevations.

The reverse is true in autumn, when nearly-bare mountaintops covered in rime ice (frozen fog) can separated from green valleys by very bright and varied leaf colors. The rhododendrons are deciduous broadleafs, whose leaves droop in order to shed wet and heavy snows that come through the region in winter.

Several rivers rise from streams in the Smokies, including the Little Pigeon River, Oconaluftee River, Nantahala River and several others. The French Broad River actually originates in the Blue Ridge Mountains, and flows through Asheville and all the way across the northeastern end of the Smokies. A Southern Railway line runs along the river as well.

Flooding can and does occur after heavy rains. In 2004, the remnants of Hurricane Frances caused major flooding, landslides, and high winds, soon followed by Hurricane Ivan which made it even worse. Other post-hurricanes, including 1989's Hurricane Hugo, have caused similar damage in the Smokies.

The culture of this area is that of Appalachia, and previously the Cherokee people. Tourism is a huge draw to the area, particularly to Pigeon Forge and Gatlinburg in Tennessee, and Cherokee, North Carolina. Rafting, either leisurely tubing or in full whitewater, is common all summer. Skiing is also done in winter, though for a short season, at places like Cataloochee and Ober Gatlinburg.

Country music legend Dolly Parton is from the Smokies, born and raised in Pigeon Forge, and lending her name to her Dollywood amusement park.