Bowyer was in the top-five most of the 50-minute session but bolted to the top of the speed chart in the final minutes behind an average lap speed of 178.059 mph.
Byron ended up second (177.223 mph) and his Hendrick Motorsports teammate Jimmie Johnson was third (177.148 mph). Ricky Stenhouse Jr. was fourth and Austin Dillon rounded out the top-five.
Las Vegas Motor Speedway has not been a particularly good track for Bowyer during his career. In 15 starts, he has one top-five and four top-10 finishes.
Rounding out the top-10 in practice were Brad Keselowski, Denny Hamlin, Ty Dillon, Daniel Suarez and Chase Elliott.
About 19 minutes into the session, the caution was displayed for debris on the track. Cars returned to action a few minutes later.
Ross Chastain was forced to sit out the final 15 minutes of practice after his No. 15 Chevrolet was late to inspection last weekend at Indianapolis.