The 449-foot bomb landed on Sheffield Avenue behind the right field wall.
Schwarber then stepped into the box to start the bottom of the first frame. Reds starter Anthony DeSclafani fell behind 2-0 in the count behind Schwarber before getting a called strike. Schwarber then blasted a 91.7-mph DeSclafani fastball well over the right field seats.
Hendricks blanked the Reds in the second and third inning, before getting some more run support. Kris Bryant hit a two-run shot in the third inning, giving Chicago a 3-0 advantage. Anthony Rizzo went yard in the next at-bat, giving the Cubs back-to-back long balls in the inning.
Yasiel Puig plated Joey Votto for the Reds' first run in the fourth inning. Chicago held a 4-1 lead entering the fifth inning.
The Reds and Cubs play the second game of the series at 2:20 p.m. Saturday in Chicago.