The Lady Bulldogs led in the third quarter before Portageville grabbed a 45-43 lead heading into the fourth quarter.
Sikeston had the lead cut to 51-49 late in the game before seeing top rebounder Martika Davis foul out.
Portageville (11-5) was able to pull away from there.
"We got into foul trouble and with the small bench we have that's going to affect us," said Sikeston coach Tiffany King.
"When Martika gets in foul trouble we lose our rebounder. We were kind of lazy today. It's hard to come out and play on a Saturday after laying around all morning."
Sikeston did get a season-high out of Robyn Morris, who scored 22 points.
Allison Blurton added 15 points followed up by Amber Minner's 12 points.
"Morris really stepped up and played for us today," said King. "I tried to get the girls to feed off Robyn."
Portageville (11-5) got a team-high 15 points from Hannah Rone. Faith Long had 14 points. Kellye Penn and Cheryl Smith added 12 and 10 points respectively.
"They were running a matchup zone against us and we couldn't put it in," said Portageville coach Eric Ellerbrook. "We finally were able to get some offensive rebounds off some missed shots. This is a nice win for us because we've lost three out of four games this week. It's been a tough week and we finally pulled one off."
Portageville will play at Chaffee on Thursday. Sikeston will host Twin Rivers on today at 6 p.m.