Ramírez appeared in Major League Baseball (MLB) as a relief pitcher for the New York Yankees (2007–2009) and Oakland Athletics (2010).

After spending the next year mastering a changeup, he spent parts of the following two seasons in independent league baseball.

Yankees backup catcher Jose Molina would later admit that he didn't remember Ramírez from their shared years in the Angels' organization.

[4] Ramírez spent his time that year learning a changeup on baseball fields in Miami, Florida, and did not pitch professionally during the 2004 season.

[2] Working with Maximo Soto, a fellow minor league pitcher released by the Angels, Ramírez developed his changeup to provide him with a new weapon in his pitching arsenal.

[5][6][7] In 43 games with Pensacola, Ramírez pitched to a 1.45 earned run average (ERA), struck out 93 batters and walked only 15.

[9][10] He pitched in one game for their Class AAA affiliate, the Salt Lake Stingers of the Pacific Coast League (PCL).

[12] Searching for a pitcher recently released by an MLB organization to fill a relief pitching role in Class A, Yankees professional scouting director Billy Eppler purchased Ramírez from Edinburg for an unreported amount of cash, estimated to be between $1,500 to $3,000.

[15] Ramírez pitched for the Tampa Yankees, their Class A-Advanced affiliate of the Florida State League, for the remainder of the 2006 season.

[8] He began the 2007 season with the Yankees' Class AA affiliate, the Trenton Thunder of the Eastern League.

[8] He was promoted to the Scranton/Wilkes-Barre Yankees of the Class AAA International League, where he pitched 26+2⁄3 innings of relief in 15 games, allowing only two runs over that span while striking out 47 strikeouts and walking nine.

He struck out all three batters he faced, including reigning American League Most Valuable Player Justin Morneau, in an 8–0 win for the Yankees.

[19] The only other rookies to strike out the side in their debut inning are Tyler Robertson, Jordan De Jong, Todd Wellemeyer, Jeremy Fikac, Braden Looper, Angelo LiPetri, and Paul Giel.

However, Yankees' manager Joe Torre had a reputation for preferring veteran relief pitchers and used Ramírez sparingly.

On 6 July, against the Angels, he gave up one run on two hits in 1+1⁄3 innings; as the pitcher of record, he was awarded his first career win in the 14–9 Yankees victory.

[18][21] In just his third relief appearance with the major league club, he faced the Tampa Bay Devil Rays on 20 July.

[22] Without control of his pitches, Ramírez walked four batters and allowed a grand slam to Dioner Navarro without recording an out.

After the game, Ramírez, shaken by his performance, cut short his comments to reporters, and was seen crying at his locker.

[26] In his first appearance with Scranton/Wilkes Barre following his demotion, Ramírez continued pitching effectively, striking out two in 1+1⁄3 hitless innings, helping Joba Chamberlain hold onto his first career Class AAA victory.

[29] The success of Ramírez and Joba Chamberlain in the bullpen convinced Yankees general manager Brian Cashman that he had enough relief pitching depth to trade Scott Proctor for Wilson Betemit.

[33][34] On 30 July, in a game against the Orioles, Ramírez intentionally threw a pitch in the area of Kevin Millar's head during the top of the seventh inning; in response, Daniel Cabrera threw a fastball near Alex Rodriguez's head in the eighth inning.

On 19 May 2009, Ramírez was optioned to Scranton/Wilkes-Barre to make room on the roster for pitcher Brian Bruney, who was activated off of the disabled list.

[44] During spring training in 2010, the Yankees signed pitcher Chan Ho Park to a one-year contract.

[48] The Athletics recalled Ramírez on 7 May and he made his seventh appearance on 12 May against Texas, allowing one run on two hits and two walks in one inning.