On April 3, 2017, Santana was the starting pitcher on Opening Day against the Kansas City Royals. He pitched seven innings, and earned the win while only allowing one run (a solo homer) and two hits. On April 15 Santana pitched a complete game one hit shutout against the White Sox, he struck out eight and walked one batter. Santana pitched another shutout against the Baltimore Orioles on May 23, followed by a third complete game shutout against the San Francisco Giants in which he threw just 91 pitches. Santana became the first pitcher in the American League to record three complete game shutouts in a season since Rick Porcello in 2014, and the first to do so prior to the All-Star break since Justin Masterson in 2013. On July 2 he was named to his second All-Star team and his first since 2008. At that time Santana had a 10–5 record with a 3.07 ERA in 111⅓ innings, while limiting opponents to a .204 batting average, second in the American League behind Chris Sale. On August 29, Santana became the 90th pitcher in history to hit 100 career batters. He finished the season 16–8 with a 3.28 ERA and 1.13 WHIP in innings, notching 167 strikeouts against 61 walks, while pacing the lead in the Major Leagues with 5 complete games (3 shutouts). He also had the lowest line drive percentage allowed (16.3%) of all major league pitchers. On November 15, Santana finished seventh in the voting for the Cy Young Award, receiving three fifth place votes. It marked the first time since 2008 Santana received Cy Young votes.