Williamsport stayed within striking distance for a while as senior forward Morgan Smith made seven of her eight foul shots in the final period.
The Wildcats lost starting center Brittany Malott when she fouled out with 3:59 to go in the game. When Williamsport coach Chris Malott questioned the call by the referee, he was given a technical foul.
Sophomore Emily Hargreaves made both of the free throws from the technical foul to extend the Leopards' lead to 38-35. That came in the middle of a scoring spurt for Hargreaves when she had nine straight points for the Leopards.
Smithsburg's lead eventually grew to six points. But Williamsport was still not out of it as Kelly Beard sank a pair of free throws to reduce the deficit to 46-42 with 1:05 left.
But the Leopards scored the final five points of the game to seal the victory, as Chelsea Hoover scored a couple of baskets and Sara Rishell made one of her two foul shots.
"Our team effort was the key to the win," said Hargreaves, who finished with a game-high 20 points. "Everybody contributed their talents to the win. I have improved my shooting over the last couple of games. It has been going in more than it has been."
Hoover scored seven of her nine points in the fourth quarter, while Rishell had 13 rebounds and eight blocked shots.
"We just tried to be aggressive and go to the basket," Smithsburg coach Ed Hargreaves said. "We were able to get out on their shooters and we pressured the ball. We kept them from getting a field goal in the fourth quarter."
Smith finished with team-high totals of 17 points and eight rebounds for Williamsport and had an impressive 12-for-13 performance from the free throw line. Beard had 13 points and Jessica Palmer had five steals for the Wildcats.
"Smithsburg kept us on the perimeter," Malott said. "We had to shoot from the outside. You have to be able to shoot the basketball. We missed too many shots."