MLB said the drug penalty was for "his use and possession of numerous forms of prohibited performance-enhancing substances, including testosterone and human growth hormone over the course of multiple years."
His penalty under the labor contract was "for attempting to cover up his violations of the program by engaging in a course of conduct intended to obstruct and frustrate the office of the commissioner's investigation."
"I am disappointed with the penalty and intend to appeal and fight this through the process," Rodriguez said in a statement. "I am eager to get back on the field and be with my teammates in Chicago tonight."
In a press conference Monday evening, Rodriguez said this has been a difficult time for him.
"I want to express to you and the fans of baseball that the last seven months has been a nightmare. Probably the worst time of my life for sure," he said, citing the "circumstances," a tough surgery and "being 38."
When questioned directly about whether he used performance-enhancing drugs, Rodriguez refused to comment.
"We'll have a forum to discuss all of that — and we'll talk about it then," he said.
When asked whether he's come to terms with the possibility that, if the appeals process doesn't go his way that his baseball career may be over, he replied: "I haven't thought that far ahead. But I am so excited to have an opportunity to wear this uniform," likely referring to the fact that if he appeals, he may be able to play during the appeal process.
The other 12 players have already agreed to their 50-game penalties.
The suspensions are thought to be the most at once for off-the-field conduct since 1921, when Commissioner Kenesaw Mountain Landis banned eight Chicago White Sox players for life for throwing the 1919 World Series against Cincinnati: Shoeless Joe Jackson, Eddie Cicotte, Happy Felsh, Chick Gandil, Fred McMullen, Charles "Swede" Risberg, Buck Weaver and Claude "Lefty" Williams. They had been suspended by the team the previous year and were penalized by baseball even though they had been acquitted of criminal charges.
(Read More: The big surprise from the Ryan Braun suspension)
As for the modern-day All-Stars, Cruz, an outfielder, leads Texas in RBIs and Peralta has been a top hitter and slick-fielding shortstop for Detroit, a pair of teams in the midst of pennant races. They will be eligible to return for the postseason.
Others agreeing included Yankees catcher Francisco Cervelli and outfielder Fernando Martinez; Philadelphia pitcher Antonio Bastardo; Seattle catcher Jesus Montero; New York Mets infielder Jordany Valdespin and outfielder Cesar Puello; Houston pitcher Sergio Escalona; and free agent pitchers Fautino De Los Santos and Jordan Norberto.
Rodriguez was the lone holdout. Baseball's drug agreement says the appeal hearing shall start no later than 20 days after the filing of the grievance and the arbitrator is charged with making a decision 25 days after the hearing starts. However, the schedule can be altered by agreement of management and the union.
Players have often succeeded at persuading arbitrators to overturn or shorten drug suspensions. In the era before the drug agreement, Lamar Hoyt, Ferguson Jenkins, Pascual Perez and Willie Wilson were among those who had success in hearings, and Steve Howe's lifetime ban for a seventh suspension related to drugs or alcohol was cut to 119 days.