The Cougars closed the game with a 19-6 run.
The win was the 10th league tournament title for the Saint Francis program since the 1994-95 season. The team's 30th win also was the most since the Cougars finished 32-6 in 200-01.
The Cougars have won 30 games five times in program history, but this was the first under 12th-year coach Gary Andrews.
Skylarr Shurn led the late-game heroics for Saint Francis, as she scored 17 of her team-leading 21 points in the second half.
Kayla Drake added 12 points in the win, which sixth consecutive victory for the Cougars.
Saint Francis swept the season against the Wildcats (30-3), whose three defeats have each been to the Cougars.
Meghan Slusher made the key play of the game for Saint Francis, as she converted a 3-point play with one minute remaining that gave the Cougars a 50-48 lead after she was fouled on an offensive put-back of her own miss, then hit the ensuing free throw.
Shurn then stole a pass and was fouled with 24 seconds to play and calmly plopped in the front end of the one-and-bonus opportunity. She nailed the second shot with ease building the Saint Francis lead to 52-48.
Kalah Baer added a steal and by the time Indiana Wesleyan fouled Jenelle Wilson, just 14 seconds remained.
Wilson coolly splashed in both charity tosses to the delight of more than 200 Saint Francis fans, who made the trip to Luckey Arena, for an insurmountable six-point lead.
Drake came up with yet another Cougar steal as time ran out and the celebration began.
The Cougar victory snapped a two-game streak of tournament titles for the Wildcats.
Saint Francis will now await the NAIA Division II National Tournament draw on Wednesday at 8 p.m.