Yankee Stadium will also host the Minnesota Twins on the Bombers' opening seven-game homestand before they make their first trip of the season, playing the Boston Red Sox from April 8-10 at Fenway Park.
New York will also keep the classic rivalry going against the Red Sox when Boston comes to town for a three-game series from May 13-15, then returns for another trio of contests from June 7-9.
Fenway Park will host the Yankees for a weekend series Aug. 5-7 and see them again for a midweek set Aug. 30-Sept. 1, before the Yankees and Red Sox end their head-to-head play with a two-game set in the Bronx Sept. 24-25.
The Yankees also renew acquaintances with the Tampa Bay Rays for the first time in a two-game series at Tropicana Field from May 16-17, in what promises to be another tough challenge ahead for the American League East title.
New York also sees the Rays for a big four-game series in New York July 7-10, heading into the All-Star Break, and then returns the favor with a four-game visit to Tropicana Field July 18-21.
The Rays come back to Yankee Stadium for a weekend set Aug. 12-14, then check into New York again for two games Sept. 20-21, before the Yankees conclude the regular season with a three-game series at the Trop Sept. 26-28.
In addition to the usual home slate of American League rivals, including numerous appearances from AL East opponents, Interleague Play will bring three National League clubs to Yankee Stadium.
The Yankees will engage the New York Mets (May 20-22) in the Bronx for the opening set of the Subway Series, then host the Colorado Rockies (June 24-26) and the Milwaukee Brewers (June 28-30).
When Interleague Play is underway in NL ballparks, the Yankees will travel to Wrigley Field (June 17-19) for the first meeting with the Cubs at the historic ballpark since 2003, surely conjuring tales of Babe Ruth's called shot in the 1932 World Series at that same site.
The Yankees also will visit the Cincinnati Reds (June 20-22) at the Great American Ballpark, in a city that has some historical significance for the Yankees -- it was there that George M. Steinbrenner declared Derek Jeter should be named team captain during a 2003 road trip.
The final rounds of the Subway Series against the Mets will be played across the Robert F. Kennedy Bridge at Citi Field (July 1-3), the Bombers' third trip to that facility.
There are two big West Coast swings on the schedule. The Yankees fly out to see the Seattle Mariners (May 27-29), Oakland Athletics (May 30-June 1) and Los Angeles Angels of Anaheim (June 3-5) in a nine-game rush, then pack up for returns to Anaheim (Sept. 9-11) and Seattle (Sept. 12-14) later in the year.
Much as it was in 2010, the final push through the end of the schedule figures to be a challenging road for the Yankees.
Their final 12 games are all against teams that provided something of a headache down the stretch this year, with the Blue Jays, Rays, Red Sox and Rays again rounding out the season's last days.