In Oakland, California, visiting Amercian League Central division champions the Minnesota Twins will take on the Amercian League West division champions the Athletics.
The Twins secured their fourth AL Central title in five years with a late run of wins to overcome the Detroit Tigers, while Oakland's last playoffs success came in 1990 when they went all the way to the World Series, only to lose to Cincinnati.
The Tigers held the AL Central lead going into the final week of regular season matches, but lost to the lowly Kansas City Royals in an extra innings to give up the Central title to Minnesota.
Detroit must now play the in-form New York Yankees in a five match series starting at Yankee Stadium, with the Bronx Bombers welcoming back Gary Sheffield and Hideki Matsui from injury to bolster a line-up already boasting the likes of Johnny Damon, Bobby Abreu and Derek Jeter.
In the National League playoffs, the Yankees' cross-town rivals the New York Mets will be looking to create a 'Subway Series' by winning the National League, but must first defeat the Los Angeles Dodgers in their five game series beginning at Shea Stadium on Wednesday.
The Mets lost star right-handed pitcher Pedro Martinez to injury late in the season, but still have a talented line-up including Jose Reyes, Carlos Beltran and David Wright, while the Dodgers have been boosted by a deadline-day transfer deal which saw starting pitcher Greg Maddux join their rotation.
In the final playoff match-up, the National League Central winning St Louis Cardinals take on NL West champions the San Diego Padres who will be relying heavily on all-time saves leader Trevor Hoffman.
The Cardinals travel to San Diego to start the series on Tuesday.