Holliday sent a towering shot to left-center off Francisco Liriano (1-2) in the third inning and Wong put it away with a drive over the Clemente Wall in right off Arquimedes Caminero in the seventh. Jhonny Peralta also homered for the Cardinals, who have won 10 of 11.
Wong finished with three hits. Trevor Rosenthal worked the ninth for his 11th save as the Cardinals improved to a major-league best 22-7. Wacha (5-0) produced six workmanlike innings, giving up three runs and six hits with one strikeout.
The Pirates have dropped six of seven and eight of 10. Liriano struck out a season-high 10 but also gave up two homers as his ERA rose from 1.93 to 2.79.
The Cardinals swept Pittsburgh in three taut games in St. Louis last weekend, winning all three on extra-inning walk-off hits despite managing just seven runs the entire weekend. They topped that number the first seven innings on Friday.
Seven of St. Louis' 11 hits went for extra bases, including two doubles by Peter Bourjos and doubles by Holliday and Wong.
Pittsburgh's sputtering offense gave Liriano an early boost when Gregory Polanco scored on an error by St. Louis third baseman Pete Kozma in the first. Peralta's fourth homer of the season clanged off the batter's eye in center field about 440 feet from home to tie it in the second. Holliday put the Cardinals up 4-1 in the fourth after Wacha reached on an error and Bourjos doubled with a blast to the deepest part of PNC Park.
The Pirates climbed within 4-3 in the sixth when McCutchen scored on a fielders' choice but the Cardinals broke it open in the seventh. Jon Jay hit a pinch-hit RBI-single to score Yadier Molina and chase Liriano. Caminero immediately gave up a double to Bourjos and Wong's third homer of the year made it 8-3.
It was more than enough as the Cardinals moved nine games clear of the Pirates, who began the season expecting to challenge St. Louis' dominant run in the NL Central after two straight wild-card finishes.
Cardinals: 3B Matt Carpenter did not travel with the team to Pittsburgh due to what manager Mike Matheny called ''extreme fatigue.'' Carpenter had a scheduled day off on Thursday - the first game he did not start all season - but could return Tuesday when St. Louis begins a series in Cleveland. ''I don't think it's a coincidence that we are in a stretch of playing 20 straight games,'' Matheny said. ''I don't think it's a coincidence that we've had a lot of tough games recently and I don't think it's a coincidence that he's as hard of a worker as there is on this team.''
Pirates: RHP Charlie Morton was dominant during a rehab start with Double-A Altoona on Friday. Morton allowed two hits in seven shutout innings, walking two and striking out five. Morton is recovering from hip surgery. His last major league start was on Sept. 16, 2014.
Cardinals: Carlos Martinez (3-0) will try to stay unbeaten when he makes his seventh start of the season for St. Louis. The 23-year-old Martinez has a 1.29 ERA on the road, the fourth-best mark in the National League.
Pirates: Vance Worley starts for the Pirates. Worley gave up one run in six innings of a no-decision against the Cardinals in his previous start last Sunday.
Link to box score: St. Louis (22-7) 8 at Pittsburgh (13-16) 5