He won 19 games and posted a 2.78 earned run average (ERA) in 2012, finishing fourth in the voting for the National League Cy Young Award and helping lead the Reds to the NL Central title.

In 2016, Cueto won 18 games with the Giants while posting a 2.79 ERA, helping lead them to the postseason, where they lost in the NLDS, and he achieved another top-10 finish in the Cy Young voting.

Cueto finished the 2010 season with a 12–7 record and a 3.64 ERA in 31 starts, pitching 185+2⁄3 innings, striking out 138 batters, but giving up only 56 walks, 19 home runs and 181 hits.

[15] Cueto started Game 1 of the National League Division Series against San Francisco, but left after only eight pitches because of a strained muscle in his back.

Cueto finished fourth in the voting for the National League Cy Young Award, behind winner R. A. Dickey, Clayton Kershaw and Gio González.

After already giving up a second-inning home run to Pirates outfielder Marlon Byrd, Cueto, who was having his name mockingly chanted by over 40,000 people, dropped the ball off the mound, much to the delight of the Pittsburgh crowd.

The Reds would show little resistance the rest of the way, and the Pirates won the game 6–2, advancing to an NLDS series with other division rival the St. Louis Cardinals.

On April 16, Cueto threw a complete game, three-hit shutout versus the Pittsburgh Pirates, striking out a career-high 12 batters without issuing a single walk.

[19] Cueto threw another complete game versus his Pirates in his next start on April 22, in which he had a shutout going until he gave up a home run to Andrew McCutchen in the ninth with one out.

He settled down to just allow the one run and another two hits, both of them singles, striking out four and walking three while throwing 117 pitches and out-dueling former Reds teammate Edinson Volquez.

[20] Cueto followed this up by throwing another shutout versus the Padres (his third complete game of the season) on May 15, striking out eight batters and allowing three singles and two walks, lowering his ERA to 1.25.

[21] In his first fifteen starts of the season, despite compiling only a 6–5 win–loss record, Cueto had a 1.92 ERA across 108 innings, with 111 strikeouts against only 26 walks, good for a WHIP of 0.83, while limiting opponents to a .169 batting average.

On July 7, Cueto had his best outing of the year against the Nationals, throwing a complete game two-hit shutout, striking out 11 batters and walking only one.

In 19 starts with the Reds, Cueto went 7–6 with a 2.62 ERA, striking out 120 batters across 130+2⁄3 innings (good for a K/9 ratio of 8.27), limiting opponents to a .196 batting average, and posting a WHIP of 0.93.

On July 26, 2015, Cueto was traded to the Kansas City Royals in exchange for Brandon Finnegan and minor leaguers John Lamb and Cody Reed.

[27] In his home debut with the Royals, Cueto threw a 4-hit complete game shutout against the Detroit Tigers, striking out eight batters without issuing a walk.

Cueto was dominant from start to finish, pitching a complete game and only gave up two hits and one run (while striking out four) to give the Royals a 7–1 victory over the New York Mets and a 2–0 series lead.

In 32 starts between the Reds and Royals, Cueto went 11–13 with a 3.44 ERA, striking out 176 batters across 212 innings, allowing just 194 hits and 46 walks, while pitching two complete game shutouts.

Cueto threw his second complete game of the season, against the Padres at Petco Park on May 18, giving up just one run on four hits, striking out eight batters and walking just two.

[34] Cueto was named National League Player of the Week for the second time in his career for May 23–29, going 2–0 with a 0.60 ERA (one earned run in 15 innings pitched), giving up eight hits, walking two and striking out 11.

Cueto became only the fourth Giants pitcher since 1958 to win 10 of his first eleven decisions on a season and the first since Tim Lincecum in 2008 (Gaylord Perry and Juan Marichal both did it in 1966).

At the time, Cueto had 12 wins against just one loss, having won nine straight decisions, compiling a 2.57 ERA across 122+1⁄3 innings, and notching 107 strikeouts against just 23 walks and 102 hits, while giving up only six home runs.

Cueto finished the year on a high note on September 29 against the Colorado Rockies, in his final start of the regular season, pitching seven strong innings in which he gave up just two earned runs on nine hits and struck out 11 batters, as the Giants won the game 7–2.

[39] Led by the strength of the pitching tandem of Cueto, Madison Bumgarner and Jeff Samardzija (who combined to go 45–25 with a 3.09 ERA in 649+2⁄3 innings with 616 strikeouts (for a K/9 rate of 8.53) across 98 starts), the Giants clinched a Wild Card berth, and defeated the New York Mets and advanced to the National League Division Series against the Chicago Cubs.

[40] Cueto finished his first regular season with the Giants with an 18–5 record and a 2.79 ERA in 219+2⁄3 innings across 32 starts, tallying a total of 198 strikeouts against 45 walks while giving up 195 hits and 15 home runs.

Cueto finished in sixth place in the voting for the National League Cy Young Award, behind Kershaw, Bumgarner, Kyle Hendricks, Jon Lester and Max Scherzer.

After revealing he had been suffering a blister on the middle finger of his pitching hand since the culmination of spring training, Cueto struck out 10 batters and allowed just two earned runs in seven innings in his second start at Great American Ballpark since leaving the Reds, his fourteenth (fifteenth counting the postseason) double digit strikeout game, and he established the record for the most double digit strikeout games by a pitcher at the stadium (eight).

He was placed on the DL on July 15 following his first start after the All-Star Break with blisters on his right hand, while later suffering a slight forearm injury in his rehab assignment.

On September 25 at Chase Field, in a 9–2 win over the Arizona Diamondbacks, Cueto struck out pinch hitting second baseman Ildemaro Vargas swinging to start the bottom of the fifth inning for his 1,500th career strikeout.

Cueto finished his outing facing the minimum of 21 batters through seven scoreless innings, giving up the one hit while striking out four and walking none as he received a no-decision in a 1–0 Giants victory.