Holliday appeared to collapse in the dugout after hobbling off the field without making it to first base.
The Cardinals' All-Star left fielder strained the same quad in pursuit of a fly ball against the Rockies on June 8 and returned on July 17, even though he had not fully regained his mobility.
Stephen Piscotty moved from first base to left field and Mark Reynolds entered at first to replace Holliday, who was hitting third in the order.
The 35-year-old's .291 batting average entering the night was the best among the Cardinals' regular players, and the injury comes two days before the non-waiver Trade Deadline and at a time when the Cardinals' offense has been struggling.