Mattituck drew to within a point early in the fourth quarter, but Weathers scored 11 points in a 21-16 finish for the Warriors (4-2).
"We run a lot and press a lot, and Kim can score in transition," Wyandanch coach Warren Fuller said.
Dejanae Mike scored eight of her 10 in the first quarter and Jessica Little sank three three-pointers to pace the Warriors early.
Mattituck, which entered the day tied with Center Moriches for first place, is 5-2.
Wyandanch, the defending Suffolk Class B champion, is now one win away from clinching a playoff berth. One more win for the Warriors, who host fourth-place Hampton Bays on Thursday, would give them five in the league guaranteeing them a .500 record and a spot in the Class B Tournament.
Wyandanch opened the season playing 10 of 12 games on the road, compiling a 7-5 record. The Warriors have started off 2-0 in their season-ending six-game homestand.
"We got a shot," Fuller said. "The attitude of the team is up. Last year, we won the league and were undefeated and [for a while] the girls weren't really used to second place."
Wyandanch is still looking up at Mattituck and Center Moriches. Before Friday's win, the Warriors had lost to each of the league leaders in overtime. Wyandanch will host Center Moriches on Feb. 8.
Said Fuller: "Any time you lose a game in overtime, you feel you can play with anyone."