On the mound, he struggled early, yielding a 5.04 ERA in his first 16 starts of the season. Wainwright pitched a three-hit, complete-game shutout and 5−0 win against Miami on July 15, 2016; the first hit he allowed was a double to Adeiny Hechavarria in the sixth inning. With four RBI against Colorado on September 20, Wainwright increased his season total to 18, the highest total for all pitchers in the designated hitter era – since 1973 – and the most since Ferguson Jenkins drove in 20 for the Cubs in 1971. On April 21, 2017, Wainwright struck out nine and hit a home run with four RBI while the Cardinals defeated the Milwaukee Brewers, 6−3. His May 27 appearance was the 330th of his career, tying him with Larry Jackson (1955−1962) for tenth place in games pitched for the Cardinals. while passing Al Hrabosky. Wainwright pitched six scoreless innings versus Los Angeles on June 1, while hitting a two-run home run facing Brandon McCarthy, for a 2−0 win. On July 17, he passed Bill Doak for fifth place in wins (145) for the Cardinals. On the same day, he became the only active major league pitcher with multiple seasons of 10+ RBI (2016–17) . The Cardinals placed Wainwright on the 10-day DL on July 25 due to mid-back tightness, retroactive to July 23. It was the fourth time in his career that he had been placed on the DL. He was activated from the DL on August 6, and totalled 11 innings in three starts. On August 18, the Cardinals placed him back on the DL for right elbow impingement. Wainwright reported pain in his right elbow for the second consecutive season and showed a precipitous drop in velocity in his latest starts. Treatments on the right elbow that Wainwright received during the season included trimming cartilage and an injection of platelet-rich plasma into the joint. In 23 games he had started, he allowed a 5.12 ERA with 12−5 W−L record. Wainwright returned to pitch on September 18 from the bullpen for the remainder of the season. In 2017, Wainwright won his first career Silver Slugger Award, the first Cardinal pitcher to win the award since Bob Forsch (1980 and 1987) and Jason Marquis (2005). He batted .262/.279/.452, a career-high .731 OPS, and two home runs.