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Weatherford's time of 19:11 was more than a minute ahead of her nearest competitor, Cloverdale's Claudia Monnett.
Greencastle's team score of 26 put the runners well ahead of second place South Putnam (72). Northview, Bloomfield and Cloverdale rounded out the field. North Putnam, with two runners, failed to qualify for a team score.
In the boys' race, Northview took the title, led by Nic Yocum's 16:33 victory.
South Putnam's Hunter Barr placed second, edging out Greencastle's Elijah Brattain with a time of 17:12.
The Eagles placed second in the team event as well, followed by Greencastle, Bloomfield, Crawfordsville, Monrovia and North Putnam. Cloverdale rounded out the field, finishing ninth.
Though Greencastle girls coach Garry Anderson was too busy running the meet to comment, the school's boys coach said he was pleased with their race.
"Overall the boys did really good," Art Dwigans said. "We started out a little bit too fast and paid for it throughout the race."
Following Weatherford in the girls race for Greencastle was fourth place finisher Kayla Cash, who clocked in at 21:01.
Brattain and Taylor Secrest led the boys team, finishing third and fourth with times of 17:18 and 17:36, respectively.
South Putnam coach Brandon Welti said he was happy with his team's day.
"I feel like they raced well and competed hard," Welti said. "We had a pretty tough week of training. I know they were racing on dead legs."
Madie Egold paced the Eagles girls, finishing 10th with a time of 22:08.
The SPHS boys top finisher was Barr, with Berndt Freeman placing seventh with a time of 17:47.
Cloverdale coach Kyle Walter said his team enjoyed the event, despite their disappointing finish.
"Our girls team as a whole competed well," Walter said. "On the boys side, Nick Blundell, a freshman of mine, gets faster every race. That outlook for the future is bright."
Blonell was the top Clover finisher, crossing at 19:06.
Cloverdale's Monnett ran her impressive second place finish in a time of 20:24.
North Putnam coach Kevin Lutes said his group enjoyed the experience.
"I was happy with how everybody did," Lutes said. "We had several people P.R."
Katie Douglas, 24:36, was the top girls finisher for the Cougars.
Dalton Spear led the boys as he finished eighth at 17:56.