Manager Ned Yost also announced the rest of his rotation Saturday. Ian Kennedy will start the second game and the April 10 home opener against Oakland. Jason Hammel, Jason Vargas and Nathan Karns will round out the rotation in that order.
Kansas City opens the season April 3 at Minnesota.
"Really a tough week," Duffy said with a laugh.
The 28-year-old Duffy returned to the Royals' camp wearing a gold medal after helping Team USA win the World Baseball Classic. He went 2-0 in the WBC.
The left-hander made 15 relief appearances last season before being inserted into the rotation on May 15. He went 12-3 in 26 starts, winning 10 straight decisions from June 11 to Aug. 21. He set a franchise record with 16 strikeouts on Aug. 1 at Tampa Bay.
"With what Danny did last year and this spring, we feel he has earned this," Yost said. "We knew this was the direction we were going to go weeks before we even showed up at spring training. We've watched Danny grow and mature to this level."
Duffy walked away from baseball during spring training in 2010 and returned on June 2. He underwent Tommy John surgery on June 13, 2012.
Yost told Duffy of his decision Friday after the pitcher allowed three runs over six innings against Seattle, but not before teasing him initially. Yost informed Duffy that Hammel would start the opener and to get ready for the third game before sharing the real plan with him.
"I just kind of let it sink in and let him make the announcement," Duffy said. "It's pretty exciting."
While Yost may have known for weeks that Duffy would be his No. 1 starter, Duffy did not take it for granted.
"There are six or seven dudes in here that could hold down that fort," Duffy said. "I'm very honored and especially being given that opportunity with the arms we have is a big deal.
"It's been a crazy ride, man. The last calendar year has been a lot of ups and downs. I've learned not to take anything for granted. I'm very, very honored. In the grand scheme of it all, we all have to go out and make 35 starts. That's the ultimate goal."