Almost two miles (3.2 km) later is an interchange with State Route 320 (SR 320), which connects to East Brainerd, and, about a half mile (0.80 km) later is a three-way interchange with the southern terminus of SR 153, a controlled-access highway that runs northwest to the Chattanooga Metropolitan Airport and crosses the Tennessee River on the Chickamauga Dam.

At this point, I-75 enters a large commercial area dominated by Hamilton Place and has an interchange with Shallowford Road about a mile (1.6 km) later.

Turning slightly northeast, the Interstate crosses a Norfolk Southern Railway, and, at exit 9, SR 317 splits off to the east.

I-75 then runs for the next several miles through a predominantly wooded and agricultural area and crossing a few ridges before reaching Cleveland at an interchange with APD-40 eastbound (US 64 Bypass [US 64 Byp.

This area is extremely susceptible to fog hazards, which obscures the visibility of drivers, and several bad accidents have occurred on this section as a result.

Running through mostly wooded and agricultural areas, I-75 reaches Athens about 15 miles (24 km) later and has an interchange with SR 30, a major east–west corridor in East Tennessee.

Around milemarker 58, I-75 enters Monroe County and, a few miles later, passes near the town of Sweetwater, containing an interchange with SR 68, another major primary state highway.

At exit 72 is an interchange with SR 72, which connects to Loudon, and, a few miles later, the highway crosses the Tennessee River on the Mitchell W. Stout Memorial Bridges.

Curving slightly to the west and then again to the east, I-75 reaches an interchange with I-40 westbound about three miles (4.8 km) later, where it begins a concurrency with I-40, and the combined routes widen to six lanes.

Traveling through a further sparsely populated rural area marked by dense woodlands, I-75 remains relatively flat for the next few miles before beginning its final major ascent, this time ascending Jellico Mountain, which in turn is part of the Pine Mountain subrange, and adding a truck climbing lane for the final time.

I-75 curves sharply to the northeast, and, about one mile (1.6 km) later, it reaches the peak of Jellico Mountain, where the truck lane ends for the final time.

I-75 remains at the peak of Jellico Mountain for approximately the next eight miles (13 km) on a segment marked by rolling hills, before beginning the transition into the Cumberland Plateau region.

[19][20] Construction of this section proved to be one of the most laborious and expensive highway projects in the state at the time, due to the massive amounts of earth and rock which had to be blasted and moved.

[27] The approximately six-mile (9.7 km) segment between SR 61 in Clinton and US 441 in Rocky Top was dedicated and opened on August 31, 1973, completing the route between Knoxville and Detroit.

[29] The last section of I-75 in Tennessee, approximately 32 miles (51 km) between SR 30 in Athens and US 321/SR 95 in Lenoir City, opened to traffic on December 20, 1974, in a ceremony officiated by then-Governor Winfield Dunn.

An approximately 10-mile (16 km) section of I-75 in northern Bradley and southern McMinn counties, including the bridge over the Hiwassee River, is prone to hazards from dense fog in the morning, which can severely obscure the visibility of drivers.

This segment is located near several heavy industries including the Resolute Forest Products paper mill, formerly Bowater, which operates settling ponds along the Interstate.

This segment has been the site of several serious multivehicle accidents, the first of which occurred on March 9, 1974, less than three months after the section opened to traffic, and before it had been declared complete.

[34] After settling with the family members of accident victims and survivors in court, TDOT instituted several safety measures along this stretch of highway, including re-striping the roadway with extra markings to make it more visible and installing a computerized fog detection system, which contains a warning system with flashing lights, electronic signs, variable speed limits, and electronic controlled swing gates which block access to the Interstate from six entrance ramps in and near this stretch in the event of dense fog.

In March 2005, the southbound lanes of Interstate 75 were shut down between milemarkers 141 to 143 due to a rockslide below the roadway that caused the pavement to partially collapse.

[39] In March 2012, the southbound lanes of the Interstate were again closed to traffic between milemarkers 141 and 143 in Campbell County, Tennessee due to a slide beneath the roadway.

The collision broke loose a chunk of concrete from a post, but engineers determined that it caused no major structural damage.

[43] On April 1, 2019, part of the bridge on I-75 southbound over the ramp from I-24 westbound to I-75 northbound at the split in Chattanooga collapsed, injuring one person and blocking traffic for hours.

TDOT first proposed to widen the concurrent segment with I-40 between the Pellissippi Parkway and I-640 to eight lanes in early 1981, which was subsequently approved by the Federal Highway Administration (FHWA) on October 9, 1986.

The first of these projects, which began in late 1998 and was completed in 2001, rebuilt the interchange with SR 153, changing the approach of two flyover ramps that connect to I-75 northbound from the left to the right side of the road.

Exit 9 was designated as the Bredesen–Ramsey Interchange in 2015 in honor of the efforts of then-Governor Phil Bredesen and county Mayor Claude Ramsey to bring Volkswagen to Chattanooga.

[54][55] On May 1, 2008, I-75 northbound traffic was rerouted back along its original path in Downtown Knoxville along I-275 as part of SmartFix 40, a major construction project that includes closing a portion of I-40.

[56][57] The project consisted of eliminating left-hand entrance and exit ramps from I-75 onto I-24, straightening curves, widening I-75 to six lanes through the interchange, widening two ramps from I-75 to I-24 to three lanes, replacing two overpass bridges, and construction of a collector–distributor facility that carries traffic directly from US 41 and the Tennessee welcome center along I-75 southbound, providing direct access to both I-75 southbound and I-24 westbound.

[58] The project was completed on August 19, 2021, at a cost of $133.5 million, making it the second-most expensive individual contract in state history at the time.

[59] In the mid-1990s, a freeway, referred to as SR 475 (with the intent of being renamed I-475), was proposed as an outer beltway around Knoxville, running north of the city between I-75/I-40 near Farragut, and I-40 near Sevierville.