Salazar was recalled from the Triple-A Columbus Clippers on July 11, 2013, and made his Major League baseball debut as the starting pitcher against the Toronto Blue Jays. He took a no-hitter into the 6th inning, striking out seven batters in six full-innings of work, the most strikeouts for an Indians' starting pitcher in his major league debut since Luis Tiant struck out eleven batters in his debut in 1964. He was optioned back to Columbus on July 12. Danny Salazar was called up to make a spot start on August 7, 2013, against the Detroit Tigers. Salazar made his first career post-season start for the Indians against the Tampa Bay Rays in the 2013 American League Wild Card Game.