Rodriguez's suspension is the equivalent of 211 regular-season games because he has 72 hours to inform MLB that he will appeal.
Major League Baseball said in a statement that Rodriguez's drug penalty was "based on his use and possession of numerous forms of prohibited performance-enhancing substances" 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."
Rodriguez returned to the big leagues hours after he was suspended through 2014 by Major League Baseball in the Biogenesis case, a punishment he plans to appeal. The three-time MVP had been out following hip surgery.
His punishment overshadowed everything else, whether it was teammate Derek Jeter going back on the disabled list because of a strained right calf or Andy Pettitte (7-9) getting knocked out early.
The crowd at U.S. Cellular Field booed Rodriguez during pregame warmups and introductions. When he stepped to the plate in the second inning, the fans could have drowned out a jet.
They weren't feeling any better after Rodriguez dropped a leadoff single into shallow left on the third pitch. He moved to third with no outs on Vernon Wells' double but was stranded.
Rodriguez flied out in his second and third at-bats and handled a few grounders at third, getting booed every time he stepped to the plate or touched the ball.
He also struck out in the eighth as fans chanted "Steroids! Steroids!"
Out of the 13 players disciplined by MLB Monday, Rodriguez was the harshest. He is baseball's highest paid star and a three-time Most Valuable Player. Twelve other players, including All-Stars Nelson Cruz, Jhonny Peralta and Everth Cabrera, were banned 50 games apiece.
The Yankees organization said it has no comment until the appeals process is complete.
"Those players who have violated the Program have created scrutiny for the vast majority of our players, who play the game the right way," said MLB Commissioner Bud Selig in a statement. "As a social institution with enormous social responsibilities, Baseball must do everything it can to maintain integrity, fairness and a level playing field. We are committed to working together with players to reiterate that performance-enhancing drugs will not be tolerated in our game."
Ryan Braun's 65-game suspension last month and previous punishments bring to 18 the total number of players disciplined for their relationship to Biogenesis of America.
The Associated Press contributed to this report.