Berkman's team-leading 23rd home run of the year was also the 350th of his career, tying him with Chili Davis for fourth place all-time among switch hitters.
The All-Star hit the first pitch he saw from Reds starter Edison Volquez deep into the right-field bleachers to give the Cards back-to-back homers and an early 2-0 advantage.
Matt Holliday had just homered to left field off Volquez, setting the stage for Berkman to deliver the Cards' fourth back-to-back home runs of the year. Berkman has been a part of all four.
Berkman's first-inning solo shot also broke Ryan Ludwick's record for the longest round-tripper at Busch III. Ludwick held the distinction of hitting the farthest homer for nearly three years after his 450-foot shot on July 22, 2008, against Milwaukee.