Byron, who had never finished better than 21st in the NASCAR Cup season opener, grabbed the lead from Ross Chastain on a restart with four of 200 laps remaining.
Byron had just taken the white flag – signalling the start of the final lap – when a multi-car wreck erupted behind him which forced NASCAR to immediately throw a caution, which froze the field.
That locked Byron into the victory in Monday’s rain-delayed ‘Great American Race’ – the 302nd Cup win for HMS.
Earlier in the race on lap 192, the contest was red-flagged when Byron hooked Brad Keselowski entering Turn 3, which sent Keselowski up the track and into Logano and triggered a huge wreck that ended up collecting 23 cars.
NASCAR red flagged the race for nearly 16 minutes to clean the track of debris. Several cars elected to pit but Chastain remained on the track and in the lead.
On the restart with four laps remaining, Chastain led the way followed by Byron, Bowman and Cindric, but Byron quickly powered to the lead after the restart before the clash that ended the race.
Watch: William Byron: ‘It sounds really good’ to be Daytona 500 winner
The win, Byron’s 11th of his career, comes on the heels of his first appearance last season in the Championship 4 competing for a series title.
“It sounds really damn good,” Byron said when asked how it feels to be called a Daytona 500 winner. “Thanks to an awesome crowd for coming out. I have so many emotions.
“Obviously hate what happened on that backstretch. I just got pushed and got sideways. But so proud of this team 40th anniversary to the day on Monday. Just extremely blessed and thankful for all the opportunities, and we just want to keep it going. We have a lot to prove this year, and this is a good start, obviously.
“Daytona 500, it’s freaking awesome. Let’s go!”
Byron credited his #24 team’s strategy throughout the race in getting him in position for the win.
“We obviously laid back and tried to save fuel for most of the race, and we would get up there at the end of the stages and make some moves, but yeah, just thankful for great power under the hood, all of our partners, Chevrolet, everybody that allows us to do this.” he said.
“I’m just a kid from racing on computers and winning the Daytona 500, I can’t believe it. I wish my dad was here. He’s sick, but this is for him, man. We’ve been through so much, and we sat up in the grandstands together and watched the race. This is so freaking cool.”
Byron’s Hendrick team-mate, Alex Bowman ended up second, with Christopher Bell in third, Corey LaJoie fourth and Bubba Wallace rallied from a late pitstop for fuel to finish fifth.
Completing the top-10 were A.J. Allmendinger, John Hunter Nemechek, Erik Jones, Noah Gragson and Chase Briscoe.