Fernando Tatis hit a double to left field in the bottom of the fifth inning, and just one batter later Eric Hosmer also struck a double into left to get the Padres on the board at 1-0.
In the bottom of the seventh, Manny Machado grounded into a fielders’ choice to score Jake Cronenworth from third. It looked as if the the Cardinals were able to snag an out from Tommy Edman tagging third, but the instant replay showed he never got his foot on the bag and the bases stayed loaded for the moment.
During the next at-bat, Hosmer was walked, which scored Grisham and crept Machado and Tatis a bit closer to home, which put he Friars up 3-0 with just two innings to go.
The final nail in the coffin came from rookie Jake Cronenworth when he raked a solo home run in the bottom of the eighth to give the Padres a four-run lead.
Closer Trevor Rosenthal came in and struck out all three batters for the Cardinals in the ninth to give San Diego their first postseason victory since 1998.
The Padres will play the Dodgers in Game 1 of the NLDS on Tuesday with game time top be announced later.