Jackson jumped up 2-0 and never trailed in the contest. Sikeston falls to 6-5-1 on the season.
"Jackson's a real tough team -- but I don't think they're four goals better than us," said Sikeston head coach Derrick Long. "We've been in a funk lately. We're leaving guys wide open and it's something that we've got to figure out. We really came out flat defensively."
Jackson's Pat Kohm and Stuart Nolen gave the Indians a 2-0 lead in the first 13 minutes of the match.
Adam Garrett provided Sikeston's only goal at the 21:00 mark on an assist from Brandon DeWitt.
It marks Garrett's 20th goal of the season, just two shy of Andrew Lawson's single-season record of 22.
"(Garrett's) got 20 of our 24 goals this year, but we're looking for a little more output from other guys," said Long. "Tanner Fritz had some good shots. We just need a few more guys to step up. Right now Adam's carrying us as far as goals."
Jackson's Matt Gordon and Kohm added two more goals late in the match to secure the win.
Chris Cota had 14 saves for the Bulldogs. Jackson out-shot Sikeston 19-18.
"It's kind of frustrating because we've been out of sync the last few days," said Long. "Hopefully we can get back on the right page."
Sikeston's junior varsity lost 1-0 to fall to 4-4-1 on the season. Sikeston will host Marion, Ill., on Thursday at 4 p.m.