Smith replaced Duffy in the fourth inning and had a career-high eight strikeouts in a dominant relief performance, helping Kansas City beat the Seattle Mariners 3-1 on Monday.
Smith (2-1) allowed one hit in 4 1/3 innings. He finished with the most strikeouts by a Royals reliever since Tom Gordon struck out eight over 4 2/3 innings against Detroit on July 9, 1993.
"Will was phenomenal, outstanding, great," Royals manager Ned Yost said. "Man, what a job he did. It was evident from some of the swings they were taking they just had a real hard time picking up the ball. His pitches had action, deception and location."
While Smith shined, Seattle ace Felix Hernandez lost his fourth consecutive start. The ace right-hander allowed three runs and six hits in 6 2/3 innings.
Hernandez departed after his back cramped up while he was pitching to Alex Gordon.
"The second pitch to Gordon I felt it cramping," Hernandez said. "It's just a cramp. It'll be OK."
Mariners manager Eric Wedge said trainer Rick Griffin told him he did not think it was serious.
Five of Smith's strikeouts took only three pitches. Kyle Seager, who had three of the Mariners' seven hits, doubled off Smith with two out in the seventh, but it was a fly ball that center fielder Jarrod Dyson lost in the sun.
"The slider was working and the curveball, too," Smith said. "It's one of those days where everything was clicking. I just kept putting zeros up."
Greg Holland pitched a one-hit ninth for his 37th save in 39 opportunities.
The Royals scored two runs in the fifth to open a 3-1 lead. Dyson led off with an infield single and advanced to third on Alcides Escobar's hit-and-run single to right. Dyson scored on a wild pitch, and Escobar came home Emilio Bonifacio's sacrifice fly.
"Speed can do a lot," Dyson said.
Hernandez (12-9), who has a 7.84 ERA in his losing streak, struck out Mike Moustakas in the sixth to reach 200 strikeouts for the fifth straight season.
Duffy, who had elbow surgery last year, departed after 3 2/3 innings and 91 pitches. He was charged with one run and five hits with four walks and four strikeouts.
"I didn't have it today," Duffy said.
"It was tough luck," Hernandez said. "A lot of ground balls to the outfield, it happens. I commanded the fastball better."
The Mariners went 1 for 11 with runners in scoring position and stranded 10 runners.
Zunino was activated from the disabled list after five rehab games with Triple-A Tacoma. He went on the disabled list July 26 with a broken left wrist. ... Carlos Pena, whom the Royals signed to a minor league contract last week, went 3 for 4 with a home run and four RBIs as Triple-A Omaha beat Round Rock to clinch the Pacific Coast League North Division championship. ... RHP Erasmo Ramirez will be added to the Mariners' roster Tuesday and start against the Royals. This will be his 10th Seattle start this season and 17th career start.