The Wildcats swept both relays and both hurdles events, as well as the 400-meter dash and triple jump, to win their first region team title since 2005.
It was a convincing victory for Wheeler, which scored 116 points to finish far ahead of runner-up Pope (79.5) and third-place Kell (76).
Milton (59) was fourth, followed by Campbell (58), Walton (54), Alpharetta (46), Roswell (45.5), Centennial (45) and Lassiter (40).
The top two finishers in each event qualified for the state meet May 13-15 in Jefferson.
Wheeler coach Cedric Sapp said his team has been gradually building towards this moment from the beginning of the season.
"It is a big accomplishment," Sapp said. "Going into the season, winning the region title was our long-term goal. We've been taking step by step. Our first goal was to win the Wheeler Relays, which we hadn't done for several years, and we did that. Our next goal was to win the Cobb County meet, and when we did that, I knew we were in a good position to win the region title."
Sapp said he and his team have had a business-like approach from the beginning of the region meet.
"I told my team that they would have to treat this meet like a business trip," Sapp said. "They treated it like a business trip and they expected to win."
It was also a memorable meet for runner-up Pope, which led after the first day and dramatically improved from last year's 10th-place finish.
"We're ecstatic," Pope coach Jerad Johnson said. "I'm proud of the way our kids fought all the way to the last event."
Leading the way for Wheeler was Jordan Thompson, who won both the 110 hurdles and the 300 hurdles.
Thompson won the 110 with a time of 14.92 seconds, ahead of Kell's Devon Williams (15.03), and was the winner of the 300 with a time of 38.78, beating Alpharetta's Drew Branch (40.10).
Wheeler was just as dominant in the relays, winning both the 400 and 1,600 relays.
The quartet of Thompson, Steven Lester, Paris Carson and Jamal Bryant won the 400 relay with a time of 41.56, beating out Campbell's team of Cory Ashburne, Javien Smith, Josh Edet and Davier Brewster (42.15).
In the 1,600 relay, Lester, Carson, Cole Jackob and Aaron Williams led the Wildcats to victory with a time of 3:19.09, finishing ahead of Campbell's foursome of Ashborne, Smith, Alan Taye and Tyshaun Smith (3:21.66).
Carson added an individual championship to his relay titles, winning the 400 dash, with Walton's Chris Foster finishing second.
Wheeler also got a win in the triple jump from Jamal Tiller, who jumped 47 feet, 9 inches to win by a convincing margin over Alpharetta's Alex Wheat (44-1).
Lassiter also won a couple of individual titles: Christian Erdman in the 800 run and Cedric Stadom in the discus.
Erdman won the 800 run with a time of 1:56.69, beating teammate David Heath (1:58.20) to complete a Trojan sweep of the two state meet berths in the 800.
Stadom won the discus with a throw of 150-8. Pope's Courtland Garrett, the runner-up in Friday's shot put, finishing second (147-6).
Kell's Shyam Kapadia was the other local winner, surging from behind to pass Milton's Tyler Tomy in the final 200 meters to win the 3,200 run in a time of 9:51.23. Tomy was second at 9:54.10.
Centennial's Martin Jenkins edged Wheeler's Steven Lester in both the 100 and 200 dashes. In the 100, Jenkins ran 10.75 to beat Lester (10.88), while Jenkins ran 21.50 in the 200 and Lester placed behind him at 22.05.