Caldwell-Pope, who has led the Bulldogs (2-4) in scoring every game this season, hit consecutive 3-pointers in the second half to help hold off the Buccaneers (1-3), who have lost three straight.
Donte Williams added 12 points for Georgia.
Freshman Lester Wilson led East Tennessee State with 12 points.
Caldwell-Pope was 5 for 9 from the field, including 3 of 6 from the 3-point line, and also led the Bulldogs with seven rebounds.
His back-to-back 3-pointers helped Georgia stop a surge from the Buccaneers, who had cut the lead to 46-35 with 6:15 left.
Georgia shot a season-high 63.2 percent (24 of 38) from the field, but was only 0 for 1 from the free-throw line.
ETSU shot 17.4 percent (4 of 23) from the field in the first half and 28 percent (14 of 50) for the game.
This was Georgia’s first game since returning from two close losses to No. 1 Indiana and No. 11 UCLA in the final two rounds of the Legends Classic in New York.
The Bulldogs, who relinquished halftime leads in both of those games, closed out the first half against ETSU on a 21-2 run. They held the Buccaneers without a field goal for the final 7:47 of the first half to lead 31-13 at the break.
ETSU led 11-10 when the Bulldogs scored 15 consecutive points for a 25-11 lead with 4:26 left in the half.
Caldwell-Pope and John Cannon sparked the run with four points each and Vincent Williams added a 3-pointer.
Wilson hit two free throws with 3:54 left, but Nemanja Djurisic and Caldwell-Pope finished the scoring with consecutive 3-pointers for a 31-13 lead.
Georgia extended the lead to 37-18 on Charles Mann’s drive and layup with 14:25 left in the game.
ETSU senior guards Sheldon Cooley and Marcus Dubose missed their second consecutive game after being suspended indefinitely. They were arrested on drug charges earlier this week.
Dubose averaged 15.5 points and Cooley averaged 9.5 points in the Buccaneers’ first two games.
As a result, ETSU started two freshmen, a redshirt freshman, a sophomore and a junior.
The Bulldogs shot 66.7 percent (14 of 21) from the field in the first half, their highest mark for one half this season.