Hitting shots from every corner of the floor, Ginobili scored 18 points in the fourth quarter, making 4 of 4 3-pointers. The Spurs went 7 of 8 on 3s and shot a blistering 78 percent (14 of 18) in the final 12 minutes.
Even when San Antonio missed, and that wasn't often, the Spurs outhustled the Cavaliers to loose balls.
Tim Duncan added 23 points and 13 rebounds for the Spurs, who completed their annual rodeo road trip at 6-3.
LeBron James scored 39 points -- 18 in the fourth quarter -- but Cleveland's superstar was again no match for the Spurs, who swept the Cavaliers in last June's finals. James added nine assists and six rebounds in 43 minutes.
Larry Hughes added 26 points for the Cavs, who went ahead 91-89 on James' 3-pointer with 5:57 remaining.
Ginobili, who was coming off a 34-point performance in a win over Toronto, has made 19 3-pointers in his past three games while helping the Spurs offset the loss of Tony Parker, who missed his eighth game in a row with a heel injury.