Rodriguez's lawyer, David Cornwell, criticized the league.
"Major League Baseball has gone well beyond the authority granted it in its Joint Drug Agreement and the Basic Agreement," he said. "Consequently, we will appeal the discipline and pursue all legal remedies available to Alex."
Before Monday's announcement, the Biogenesis scandal had already ensnared one star: 2011 National League MVP and Milwaukee Brewers outfielder Ryan Braun.
Last month, Braun was suspended without pay for the rest of this season for violating the league's drug policy.
Yankees: We're "focused on playing baseball"
The New York Yankees declined to comment on Rodriguez's suspension until the completion of the appeal process.
"In the meantime," the team said in a written statement, "the Yankees remain focused on playing baseball."
The team did say it was disappointed by the suspension of Yankees catcher Francisco Cervelli, who was one of the 12 players who agreed to the 50-game suspension.
"It's clear that he used bad judgment," the Yankees said.
Major League Baseball issued a statement saying that Rodriguez was being disciplined under both baseball's Joint Drug Prevention and Treatment Program and the players' collective bargaining agreement.
Under the drug program, "Rodriguez's suspension will be stayed until the completion of his appeal if Rodriguez files a grievance challenging his discipline," the MLB statement said.
That is also the usual case for suspensions related to drug offenses under the collective bargaining agreement, but the statement did not specifically address that aspect.
Rodriguez is considered one of the game's greatest sluggers. He has 647 home runs -- the fifth most ever -- in 19 seasons.
In 2009, he had an outstanding postseason as he helped the Yankees win their most recent World Series title.
He holds the largest contract ever in American sports, signing with the Yankees in 2007 for $275 million over 10 years.
Rodriguez said Friday he believes his contract makes him an attractive target for a baseball ban or suspension.
"There's more than one party that benefits from me not ever stepping back on the field -- and that's not my teammates and it's not the Yankees fans," he said.
Rodriguez has missed the entire 2013 season so far after undergoing hip surgery.
Other players suspended
The other players suspended by Major League Baseball Monday are:
Philadelphia Phillies pitcher Antonio Bastardo
San Diego Padres shortstop Everth Cabrera
New York Yankees catcher Francisco Cervelli
Texas Rangers outfielder Nelson Cruz