The Lady Bulldogs were blitzed by the state-ranked Lady Lions for 20 first-quarter points in a 67-35 loss on Thursday afternoon.
Tuscumbia - No. 6 in the inaugural MBCA/MOsports.com Class 1 poll - carried a 13-point advantage after a quarter of its season opener.
South Callaway (2-1) was outscored 23-13 in the second quarter to trail 43-20 at halftime.
"Defensively, we played pretty well, they just absolutely shoot the lights out of the ball," Lady Bulldogs head coach Darren Humphrey said. "Their shooting percentage was unbelievable and that set the tone for the game.
"...Their pressure kind of got to us a little bit and they shot the ball well enough to absolutely put on a show."
Junior guard Sarah Jennings sparked South Callaway with nine points. Sophomore center Konnor Arrowood and freshman point guard Adrian Mann added eight points each.
The Lady Lions were led by Kendra Vaughn's game-high 17 points. Sisters TaKayla and Tempary Gunter scored 16 and 15 points, respectively.
The Lady Bulldogs play at Hallsville at 6 p.m. Monday.