The Angels exercised Santana's $13 million option for next season before trading the Dominican veteran and cash to the Royals.
"We're proud to have him, and he certainly fits with what we're doing in 2013," Royals general manager Dayton Moore said.
Santana has been a fixture in Los Angeles' rotation since 2005, going 96-80 with a 4.33 ERA while starting at least 23 games in eight consecutive seasons. He has spent his entire career with the Angels, who signed him as a free agent in 2000 and nurtured his development into a solid starter of 96 games over the past three years.
But Santana struggled for much of last season, going 9-13 with a 5.16 ERA while giving up a major league-worst 39 homers despite significant improvements over the final two months. Santana's woes and Dan Haren's similarly slow start were major factors in the Angels' midseason struggles, forcing Los Angeles to make a trade for Zack Greinke and ultimately keeping them out of the playoffs for the third straight season.
With rising starter Garrett Richards already slated for the Angels' rotation in 2013, Santana has long realized he might be headed out of Orange County after the season.
"I have to realize that this is a business," Santana said, citing Kauffman Stadium as one of his favorites in the majors. "They trade me, and I just have to accept it and move on. It's going to be hard because I've known my teammates for a long time, but now I'm going to have new teammates. I can't wait to meet them in person and hang out."
The Royals made a similar deal last November for Jonathan Sanchez, giving up Melky Cabrera for the San Francisco starter who was expected to anchor their rotation. But Sanchez was a disastrous flameout, going 1-6 with a 7.76 ERA in just 12 starts before getting designated for assignment and eventually traded to Colorado.
Moore wasn't shy about dealing for Santana with just a year left on his contract, saying he hadn't discussed a long-term extension with the right-hander.
"We were able to scout Ervin during the entire year, specifically the second half," Moore said. "His August and September were really good. From a statistical standpoint, he was very good."
Moore said the Royals are paying "the majority" of Santana's $13 million deal.
Santana, who will turn 30 in December, has shown moments of brilliance in his career, which includes three seasons with at least 16 victories and an All-Star selection in 2008. He threw a no-hitter in 2011 and a one-hitter last season, yet confounded the Angels with his inconsistencies early in 2012.
"I don't have any physical problems," Santana said. "Everything was good. I just have bad luck. I was pitching good, and I didn't have the opportunity to win a lot of games."
The Angels are more interested in developing Richards and attempting to re-sign Greinke, who pitched well during his brief stint with Los Angeles. Ace Jered Weaver will top the rotation after his first 20-win season.
The Angels haven't announced whether they'll pick up Haren's $15.5 million option for next season before Friday's deadline. The club is thought to be shopping Haren, who had a career-worst 4.33 ERA while going on the disabled list for the first time.
Sisk spent last season with Triple-A Omaha, going 3-2 with a 2.54 ERA and eight saves. He's pitching in the Venezuelan winter league and has never pitched in the majors.