Chen re-signed a minor league contract with the Royals on December 11, 2009. On April 26, 2010, he earned his first MLB save, in a 3–1 Royals victory over the Seattle Mariners. He threw seven perfect innings before allowing a hit on July 20, 2010 against the Los Angeles Angels. On October 1, 2010, in his last start of the season, Chen threw a two-hit shutout against the Tampa Bay Rays, striking out seven and only walking two. It was the first shutout he threw in his Major League career. He finished the season with a 12–7 record, and an ERA of 4.17.