Ginobili, inserted into the starting lineup for the first time all season, totaled 24 points and 10 assists and has the Spurs one win away from their fifth championship since 1999.
All five starters scored in double figures for the Spurs, who never trailed and ran the Heat out of AT&T Center with a high-paced style and a 60 percent shooting effort.
Danny Green continued to shoot the lights out, as the up-and-coming gunner poured in 24 points and hit six more 3-pointers to set a Finals record with 25 already this series.
Tony Parker shook off a hamstring injury and put up 26 points, while Tim Duncan added a typical 17-point, 12-rebound showing.
Kawhi Leonard chipped in 16 points and eight boards and did another terrific job guarding league MVP LeBron James, who had 25 points but needed 22 shots to do so.
Dwyane Wade checked in with 25 points and 10 assists, and Chris Bosh logged 16 points for the Heat, who got little production from role players not named Ray Allen.
The defending champions host Game 6 on Tuesday with the knowledge they have not lost back-to-back games since January. Broadcast coverage starts at 5pm, tip off at 8pm on 1200 WOAI.