The 26-year-old Vandeweghe beat world number one Simona Halep and U.S. Open champion Sloane Stephens earlier in the tournament but could not find a way past Pliskova.
"It's the best atmosphere to play in Germany," Pliskova said after the match. "I want to thank my team. I think we had a great week and without them I would not have the trophy."
Former world number one Pliskova trailed 2-0 in the tiebreak at the end of a tight first set but reeled off seven points in a row for an early advantage in the contest.
After Vandeweghe called for the trainer following a tumble early in the second set, Pliskova raised her level and broke her bruised opponent's serve to go up 3-2.
Pliskova saved a breakpoint in the next game to increase her lead. She then broke Vandeweghe again to make it 5-2 before the American attempted a late fightback with a break of her own.
Pliskova, however, maintained focus to serve out the match.
Victory in Stuttgart gave world number six Pliskova a 10th career title and her first since winning the trophy in Eastbourne last year.
(Reporting by Shrivathsa Sridhar in Bengaluru; Editing by Toby Davis)
