The Bulldogs (9-5) led by just seven points at halftime, but the team opened up a double-figure lead early in the third quarter and maintained it the rest of the game.
Sikeston coach Gregg Holifield said he was concerned with a potential letdown after Friday night's emotional victory against arch rival Charleston.
"I thought offensively we really played well -- we were very unselfish and we hit the open man and shot the basketball well," said Holifield.
"There were times we played good defense and other times we had some breakdowns. Overall after a very emotional game Friday night, this is a good road win for us."
Sikeston trailed 15-11 in the first quarter on the hot shooting of Fredericktown guard Dustin Bess, who sank three 3-pointers in the first quarter.
But Sikeston rallied to take an 18-15 lead at the end of one.
Fredericktown (8-6) stayed close in the second quarter, but couldn't get any closer than five points as Sikeston took a 39-32 lead into halftime.
"They've got good players and they shoot it so well from the perimeter," said Holifield. "Bess made some 3-pointers early in the game to keep them close. They're so well-coached and (coach Brett Reutzel) gets so much out of what they do."
The Bulldogs opened up a double figure lead in the third quarter and took a 60-47 advantage into the fourth quarter.
After hitting four 3-pointers in the first half, the Blackcats were limited to just one longball in the second half, which came late when the game was out of reach.
The Bulldogs cruised the rest of the way as Fredericktown never got closer than 13 points.
"I might get chastised for saying this, but I think the style and the level of play is different between the two areas," said Reutzel. "We're not used to playing at that high a level all the time. I'm sure a little fatigue set in. I don't think we're necessarily out of shape, but to play four quarters at that pace against that kind of competition, I think you really have to be sharp."
Sikeston spread the scoring out as senior guard Julian Beard had 20 points (8-10 shooting) with a season-high seven assists and three steals.
Sophomore Michael Porter had 20 points with three blocked shots.
Senior guard Blake Taylor had a season-high 19 points with 16 of those coming in the second half. Taylor scored a career-high 23 points against Fredericktown last season.
Senior Isaac Porter had all 13 of his points in the first half to go with his five steals. He was 5-5 from the field.
"I thought Isaac Porter really played well in the first half and kind of carried us there, and then Blake really played well in the second half," said Holifield. "Julian and Michael were very consistent tonight."
Junior Brandon Washington continued to make good use of his starting role as he scored eight points with a team-high seven rebounds, four assists and three steals with a charge drawn.
Bess led Fredericktown with 20 points. Eli Skaggs had 13 points and Jerod Williams chipped in with 10 points.
"We knew they would compete and battle -- they always do," said Holifield. "We were able to build a lead in the second half and we did that with shot selection more than anything. Defensively we got a few stops there to help build the lead."
The Bulldogs were 35-56 from the field for a sizzling 63 percent shooting rate.
"They're exceptionally talented -- I have the upmost respect for coach Holifield and I always have," said Reutzel. "We've had a very friendly rivalry for a lot of years while I was at Cape, and now here at Fredericktown I think we've resumed that. He runs a class operation and a class program. His kids play hard for him and they're a very talented team."
Sikeston will play at Scott City on Friday at 6 p.m. Fredericktown will host Ste. Genevieve on Friday.
The Sikeston J.V. team improved to 8-3 on the season with its fifth straight victory, defeating Fredericktown 76-33.
Sikeston bolted out to a 21-8 first quarter lead and a 38-19 halftime lead. The Bulldogs led 59-27 heading into the fourth quarter.
Sikeston was led by Dominic Fondon's 20 points, nine rebounds and four blocked shots.
Freshman Eli Jackson had 16 points, seven rebounds and five assists.
Freshman Juqualin Wiggins had a season-high 13 assists with five rebounds. Sherwin Jones had nine points and three steals.
Luke Cureton had 12 points to lead Fredericktown.