Byron, who had not finished better than 14th in the past five races, left little doubt in Sunday’s race, leading 66 of the 90 laps.
Byron cycled into the lead following an early caution in the final stage for team-mate Chase Elliott’s stalled car and cruised to a 2.632-second win over polesitter Denny Hamlin.
The victory for the #24 Hendrick Motorsports driver is a series-leading fifth triumph of the season and the ninth of his career. It’s also his first road course victory in the Cup series.
Hamlin, just ahead of Byron in the regular season standings, had to settle for second place ahead of fellow playoff contender Christopher Bell.
A.J. Allmendinger and Ty Gibbs, who still hold an outside shot of the playoffs, could only manage fourth and fifth respectively.
Overall points leader Martin Truex Jr came home in sixth ahead of a quartet of fellow playoff contenders Chris Buescher, Tyler Reddick, Ryan Blaney and Joey Logano.
Next Saturday night’s race at Daytona International Speedway is the final race in which a driver can win his way into the playoffs.
"Just a huge credit to the race team behind me. I want to thank Max Papis. This first road course win - we've worked years and years for this," Byron said. "Thanks to him. I know he's watching back home.
"I think it shows that when we're at our best, we can perform like this. We seem to go through that summer slump in July and August, and for some reason we just can't quite put the races together. I think it's the race tracks itself.
"Road courses have been tough, so it's fun to get a win."
Elliott’s season continued to underdeliver as he stopped on track on lap 53 when he ran out of fuel in his #9 Hendricks Motorsport Chevrolet, which caused a three-lap caution period.
It meant the 2020 NASCAR Cup champion must now win the final race of the regular season to make the playoffs.
NASCAR Cup - Watkins Glen race results
