George scored nine of his 22 points in the third quarter, during which the Pistons outscored Portland 31-14.
Indiana has recorded back-to-back victories to move one game above the .500 mark. Going into Wednesday night's action no member of the NBA's Central Division had a winning record. Portland had won its previous two games.
After trailing by 15 to start the fourth period, the Trail Blazers rushed back to within four midway through stanza. Indiana reopened a nine-point lead and held on from there.
Damian Lillard led Portland with 26 points, six assists and four rebounds. LaMarcus Aldridge contributed 18 points and 10 boards.