The result represented steady progress from 26th at the start of a hot afternoon in Nashville, while Nemechek and Joe Gibbs Racing team-mate Chandler Smith ran away with the 188-lap contest.
Pole-sitter Ty Gibbs (#19 JGR Toyota) led initially, from series leader Cole Custer (#00 Stewart-Haas Racing Ford) and AJ Allmendinger (#16 Kaulig Racing Chevrolet).
Van Gisbergen (#97 Kaulig Chevrolet) had qualified 28th-fastest and took the green flag in 26th, but dropped outside the top 30 by Lap 9.
Gibbs led by more than three seconds when Allmendinger passed Custer for second place at the start of Lap 32, as van Gisbergen ran 28th.
When Stage 1 ended on Lap 45, Gibbs was out in front, albeit by less than two seconds, with Allmendinger second, from Brandon Jones (#9 JR Motorsports Chevrolet) and Custer, and van Gisbergen 27th.
The pit stops shook things up, with Custer taking the lead and the #19 Toyota dropping to fourth for the Lap 53 restart, while the #97 Chevrolet sat 21st.
Custer duly led the field back to green as Gibbs took up second place for Stage 2, before he was passed by JGR team-mate John Hunter Nemechek (#20 Toyota) on Lap 64.
Nemechek went under Custer for first place at Turn 1 on Lap 71, by which time Allmendinger had prised third spot from Gibbs.
Van Gisbergen, meanwhile, had crept up to 19th as he raced with Kaulig team-mate Josh Williams (#11 Chevrolet).
Allmendinger overtook Custer for second place at Turn 1 on Lap 85 but was unable to make much of an impression on the two-second lead enjoyed by Nemechek, who clinched the stage victory on Lap 90.
Custer was third and Gibbs fourth, while van Gisbergen had prevailed in the battle with Williams for 18th with a Lap 86 pass.
Nemechek retained the lead through pit lane but Allmendinger lost second lace to Custer, with van Gisbergen in 21st.
The restart came on Lap 98 and Nemechek led Custer away while Allmendinger took third from Gibbs on Lap 99.
Van Gisbergen briefly dropped as low as 24th but was soon back up to 19th position, as Custer passed Nemechek for top spot through Turn 4 on Lap 102.
When Nemechek had a moment on Lap 114, Allmendinger capitalised with a pass for second place at Turn 4 and then set about erasing the #00 Ford’s second-plus margin.
He quickly halved it but then his progress stalled, while van Gisbergen had moved up to 17th on Lap 127, and Nemecheck passed Gibbs for third on Lap 131.
A Caution was called on Lap 135 when Justin Allgaier (#7 JRM Chevrolet) tipped Gibbs into a spin at Turn 4 in their battle for fourth.
With the critical lap having been reached, all of the front-runners were into the lane under yellow.
Custer still led off, from Nemechek, Chandler Smith (#81 JGR Toyota), and Austin Hill (#21 Richard Childress Racing Chevrolet), but Allmendinger plummeted to ninth, with van Gisbergen up to 15th.
The race went green again on Lap 143 and Custer made a good launch but then slid high.
Nemechek assumed the lead, from Chandler Smith, Hill, and Noah Gragson (#30 Rette Jones Racing Ford), with Custer dropping to fifth by the time he had settled.
Van Gisbergen dropped to 18th but managed to rise to 14th on Lap 153 after prevailing in a battle with Parker Kligerman (#48 Big Machine Racing Chevrolet), then slipped back to 16th as Brandon Jones and Allgaier climbed through the field after earlier dramas.
JGR Toyota drivers Nemechek and Smith cleared out to a six-second lead over the field but Custer was going the other way and he was rounded up by Allmendinger for seventh position on Lap 161.
By the time Jesse Love (#2 Chevrolet) went under RCR team-mate Hill for third place on Lap 181, he was eight seconds behind Chandler Smith, who had drifted more than a second in arrears of Nemechek.
When the chequered flag flew on Lap 188, Nemechek won by 0.366s, with Love another eight seconds back, from Hill, and Gragson.
Allmendinger finished seventh, van Gisbergen inherited 15th when Sheldon Creed (#18 JGR Toyota) had to make a late pit stop due to electrical problems, and Williams finished a lap down in 24th in the third of the Kaulig Chevrolets.
NASCAR returns to the Chicago Street Circuit next weekend, when 2023 Cup race winner van Gisbergen will be on double duty.
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