Busch ended Jimmie Johnson's three-race winning streak at Texas, getting his 36th Sprint Cup victory a week after also winning at Martinsville.
Busch also won the Xfinity race at Texas on Friday night, his 80th win in that series that was coming off a two-week break. At Martinsville, he also got his 45th Camping World Truck Series victory. That's four NASCAR Series wins in a span of eight days.
On the first lap after the final restart, lap 302 of 334, Busch went on the outside of Turn 4 to shoot around Martin Truex Jr. for the lead. Busch led the rest of the way in his No. 18 Joe Gibbs Racing Toyota, winning by nearly 4 seconds over Dale Earnhardt Jr. with Joey Logano third.
It was Busch's second Sprint Cup victory at Texas, where in 2013 he also swept both spring races.
NASCAR's first night race of the season actually went into the next morning, ending a few minutes after midnight Texas time after the start was delayed for 1 hour, 50 minutes while drying the track after a couple of light rain showers during the afternoon.
Johnson, who had won five of the previous seven Texas races, finished fourth. When the Sprint Cup Series returns to Texas in November, he will be trying to win the fall race there for the fifth year in a row.
Chase Elliott, Johnson's rookie teammate with Hendrick Motorsports, finished fifth. Elliott has qualified fourth, but had to start at the back of the 40-car field after a transmission change in the No. 24 Chevrolet.
Edwards led 124 laps and was running second on a restart with 113 laps to go after pitting during a caution. Within a few laps after that, he had to go back in the pits because of a loose front right wheel and dropped all the way to 19th. He has won three Cup races at Texas, the last when sweeping the 2008 races.
Truex led six times for 141 laps.