Joined by team-mates Kyle Larson and Alex Bowman, it was an all-Hendrick Motorsports podium in Las Vegas.
Lining up on the outside of Martin Truex Jnr with fresher tyres for the final restart, he was able to make the move stick after a perfect pit stop from his crew.
Aric Almirola caused that Caution, spinning into the wall in an incident that re-shuffled the field with three laps to go and set the race into overtime.
Byron finished the race after leading 176 laps in Sin City, never leaving top four in the running order as he clinched the third win in a row for Chevrolet.
“Yeah, just been really confident about the group of guys that I have on this 24 team,” said Byron.
“They work extremely hard, and we spent a lot of time in the off-season just going through running at the sim [simulator] with Chevy and running on iRacing and just trying to get better as a race car driver and as a team.
“Thinking of Chase back home. Wish he was out here with us. He's a great race car driver, great teammate.”
In the fourth Hendrick Motorsports entry, Chase Elliott was replaced by Josh Berry, who finished in 29th in his first race driving a Next Gen car.
Elliott suffered a fractured tibia in a snowboarding accident in Colorado on Friday and while surgery is said to have been successful, the team has given no timeline for his return behind the wheel of the #9 car.
Toyota drivers Bubba Wallace and Christopher Bell rounded out the top five in Las Vegas.
Pole-sitter Joey Logano brought out a Caution on Lap 182 when he slid through the infield after contact with Brad Keselowski.
He retired and finished with a last place result.
The 2023 Cup Series season wraps up the West Coast swing at Phoenix Raceway next weekend on March 12, starting at 15:30 ET/06:30 AEDT.