In 10 regular season starts for the Cardinals, Lackey allowed two or fewer runs in seven of them. He totaled a 3–3 W–L with a 4.30 ERA in 60 ⁄3 IP with St. Louis, and his totals for the year including those with Boston were 14-10 W–L with a 3.82 ERA and 164 strikeouts in 198 innings. He made the postseason for the seventh time in his career, starting once each against the Los Angeles Dodgers in the National League Division Series (NLDS) and the San Francisco Giants in the National League Championship Series (NLCS). The Giants defeated the Cardinals in five games, ending their season. Instead of retiring and foregoing being paid the league minimum, Lackey had stated in the previous August that he would pitch in 2015 if the Cardinals picked up the option that actuated because he missed the 2012 season due to Tommy John surgery. On October 30, the Cardinals announced they had picked up the Tommy John option. With a guaranteed base salary of $507,000, the club added performance bonuses before the start of the season.
In 7 ⁄3 IP against the Chicago Cubs on May 7, 2015, Lackey struck out 10. He also drove in his third career run with a double, his third career extra base hit in a 5–1 win. On July 12, despite the Cardinals losing to the Pittsburgh Pirates 6–5 in 14 innings, he achieved his sixth consecutive quality start, and 12th in 15 appearances. He lost to the Cincinnati Reds on July 29, but gave up just one run with eight strikeouts while allowing one walk and two hits. It was the fewest hits he allowed through that point in the season. He also allowed three runs or fewer in all but of one of his prior 17 starts.
On December 8, 2015, Lackey signed a two-year, $32 million contract with the Chicago Cubs.
Lackey resides in the Austin area in the off-season. He and his wife, Kristina Carter, had their first child, a daughter, in November 2015. John is stepfather to Carter and Mavi, Kristina's children from her first marriage.