Down 10 with just over four minutes to play in regulation, Midwestern State battled all way back to force overtime on Monzaigo Williams' 3-pointer from the left corner in the closing seconds.
But the Mustangs ran out of gas as Arkansas Tech's Bobby Hatchett knocked down 14-of-18 shots from the charity stripe to finish with a game-high 22 points to lead the Wonder Boys to a 75-73 win.
The loss snapped MSU's 19-game home court winning streak at D.L. Ligon Coliseum as the Mustangs suffered just its third loss under the dome since the start of the 2008-09 season.
Midwestern (6-3) returns to action Monday night when it plays host to Mid-America Christian. Tip off is set for 7 p.m.
For the fifth consecutive game, the Mustangs faced a double-figure deficit in the first half. The lengthy ATU squad used a 2-3 zone to limit MSU to 7-of-27 shooting (25.9 percent) in the opening half as the Mustangs didn't hit double digits until Kevin Grayer knocked down a 3-ball with just under five minutes before halftime.
Before that, it was all Wonder Boys as senior forward Will Paul scored 11 of his 17 points in the opening half as ATU led by as many as 16 points before the Mustangs closed the half on a 9-2 run culminated by Corbin Thomas' thunderous dunk right before the buzzer to pull MSU to within 29-21 at the half.
Thomas completed his third double-double of the season with 20 points and 13 boards including 10 on the offensive end. He would three blocks and a steal in 43 minutes of action.
Midwestern chipped away at the lead narrowing the margin to 42-39 on a Williams' trey with 7:56 to play, but the Wonder Boys answered with a 9-2 run to re-establish a 51-41 lead with 4:13 remaining in regulation.
Kevin Grayer connected on a 3-pointer and Thomas tipped in an impossible bucket to cut the lead to 53-51 with 33 seconds to play.
After Paul went 1-of-2 from the free-throw line, Grayer misfired on a 3-pointer but sophomore Derrell Gibbs snared a rebound and delivered a pass to Williams who was spotted up in the corner for the tying shot.
The Mustangs claimed their first lead of the game on a Thomas layup with 3:15 to play in the first overtime, but still MSU needed a pair of clutch conversions at the charity stripe from Grayer late in the period to force another session.
MSU led by as many as four points in the second overtime, but couldn't manage field goal after Cameron Adderley's jumper from the elbow gave the Mustangs a 70-69 lead with 1:38 to play.
Arkansas Tech combined to hit 5-of-6 from the free throw line in the final 10 seconds to preserve the victory.
Williams finished with 14 points, six assists and two steals before fouling out in 45 minutes, while Grayer had 15 points and four rebounds off of the bench.
Arkansas Tech improved to 4-4 on the season.
Texas-Permian Basin buried its first 12 shots from the field Saturday afternoon at D.L. Ligon Coliseum.
But Midwestern State stayed the course, remained closed before stepping the gas to roll past the Falcons 76-61 to improve to 7-1 on the season.
The Mustangs take on former Lone Star Conference foe Central Oklahoma Wednesday at Hamilton Fieldhouse in Edmond. Tipoff is set for 6 p.m.
Sophomore guard Shatoia Gober poured in a career-best 18 points on 8-of-12 shooting including 14 in the first half when the Mustangs trailed by as many as seven points.
MSU outscored the Falcons 20-5 over the final 8:25 of the first half getting substantial contributions from sophomore forward Taylor Dowd and redshirt-freshman forward Katie Brown, who combined for six points over the final three minutes of the half as the Mustangs constructed a 42-32 advantage at the intermission.
Sophomore forward Andrea Carter led the charge in the second half nearing a double-double with 10 points and nine rebounds over the final 20 minutes alone on her way to a 16-point, 12-rebound outing.
Led by Taniqua Ards' 20-point effort, UTPB pulled to within 42-37 less than a minute into the second half, but the Mustangs would push the advantage back to double figures and maintain the lead for much of the second half.
The Mustangs led by as many as 15 points when Carter knocked down a free throw to give MSU a 74-59 advantage with 1:49 to play.
Junior guard Kirsti Degelia connected on all eight of her free throws on her way to a 12-point, 5-assist outing while Ashley Rush and Taylor Dowd added seven points each.
Teisha King added 16 points for Texas-Permian Basin who fell to 6-3 on the season.