Take the Uptown A or C (of the A-C-E, the blue line) from 34th Street-Penn Station to 59th Street-Columbus Circle. At 59th Street-Columbus Circle, transfer to the Uptown B or D trains. Take the Uptown B or D to 161st Street-Yankee Stadium.
The Bronx-bound D train does not stop at Yankee Stadium on weekdays from 4 to 6:45 PM, so if you are traveling during those times, you need to take the B.
Don't take the B unless you are traveling on a weekday between 4 and 6:45 PM, because the B only stops at Yankee Stadium when the D isn't stopping there.
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Take the Downtown B or D trains (of the B-D-F-M, the orange line) from 161st Street-Yankee Stadium to 59th Street-Columbus Circle. Transfer at 59th Street-Columbus Circle to the Downtown A or C trains to 34th Street-Penn Station.