The Dragons snapped a five-game losing streak to Sikeston with Saturday's win.
For the third straight time the Bulldogs got way behind early and could not recover.
DeSoto raced out to a 28-4 lead and they never looked back.
Sikeston rallied in the second half, but never could get closer than 11 points.
Sikeston actually out-scored the Dragons 48-46 after the first quarter, but the huge edge in the opening frame was too much to overcome.
"I thought we played very well at the start of the second quarter," said Sikeston head coach Gregg Holifield. "We competed and out-scored them from that point on. But again we dug a big hole and got behind and we're trying to battle out of it. We have to be more aggressive at the start of the game."
DeSoto, sporting a frontline of 6-foot-8 and 6-foot-7, simply dwarfed the smaller Bulldogs.
The sheer size of the Dragons seemed to intimidate Sikeston from the start as they raced out to a 10-0 lead, all on offensive putbacks.
"They really hurt us on the boards," said Holifield. "Their first 10 points were scored on second and third shots. You just can't beat good teams like that. They had the 6-8 and 6-7 kids that are good players. Plus they're very strong. They knocked us around and pushed us around and they kept us from doing what we wanted to do."
Tony Boyle and Anthony Thebeau, the Dragons' two post players, combined to score 14 of the team's 21 first quarter points as they led 21-4 after one quarter.
DeSoto led by as much as 33-8 in the second quarter before the Bulldogs woke up to close the half strong. Johnny Bland scored all seven of his points in the second quarter to help the Bulldogs trim the lead to 36-18 by halftime.
The Bulldogs continued the momentum in the third quarter, cutting the lead to 38-26 on a Nate Thomas shot.
Sikeston got as close as 40-29 and 44-33 but that was as close as they would get.
DeSoto led 52-36 entering the fourth quarter.
Boyle led all scorers with 21 points. Josh McCullough followed up with 16 points, including three 3-pointers. Thebeau added nine points.
It was DeSoto's home opener in front of a loud, raucous crowd.
"They were on their home court, they're a final four team from last year and they returned several players," said Holifield. "That's two tough places to play. You go into Dexter with our young team and then the very next night you're at DeSoto. You're playing against all odds there to start with. We just need to come out and be aggressive and take control of the game. But I will say this about our players, they continue to work and battle. They show no signs of quitting. We're just going to work and try to improve."
Sikeston was led by Thomas' 12 points with three steals.
Freshman Joe Lincoln got this first start and contributed nine points, while getting a pair of steals.
The loss ends the Bulldogs' impressive run against an always-tough DeSoto team, last losing to the Dragons in 1997. Overall, Sikeston has won six of the eight meetings between the two.
Sikeston will play New Madrid County Central on Tuesday at 7:30 in the Sikeston Invitational Tournament.
Sikeston had to battle, but a big fourth quarter propelled the jayvee Bulldogs to 6-0 on the season with a 70-53 win against DeSoto's JV.
Sikeston led 13-12 after one quarter and 28-27 at halftime. They extended the lead to 46-43 entering the fourth quarter before exploding for 24 points in the final frame to put the game away.
Sophomore Trey Spence had a season-high 27 points with 14 rebounds and three steals on 13-of-20 shooting. He scored 15 of his points in the fourth quarter.
Sophomore Kash Bratcher followed up with 14 points with six rebounds and five assists.
Freshman Julian Beard added 12 points. Joel Nabors grabbed seven rebounds. B.J. Green, Rod Moore and Jeremy Conley each had three steals. Green also had three assists.