The second baseball game released for Wii features 30 professional teams, authentic stadiums, and hundreds of real-life players. Major League Baseball 2K8 also offers motion-sensitive controls on the mound, in the field, and at the plate. Pitching involves pointing the Wii Remote at the screen to set location and the Wii Nunchuk to choose pitch type. The throw involves holding down a button, tilting the Wii Remote back, and flicking it forward as an onscreen cursor falls within a bull's eye target. A throw's accuracy is not only influenced by timing, but also from a pitcher's statistical ratings from the 2007 season.

Batting involves a timing-based system as well, where players hold the Wii Remote upright and swing it like a real bat, only without the follow-through. Speed influences power, so players can vary the types of hits by adjusting how fast they move the Wii Remote. The analog stick is used to adjust the bat's direction for ground or fly balls. Check swings are possible, and players can even twirl the controller to move the onscreen bat before the pitch crosses the plate. Fielding is primarily controlled with the analog stick, with the Wii Remote used to perform dives and jumps. Throwing is either automatic or manually controlled.

MLB 2K8 for Wii also includes in-depth franchise options, where players manage front office details like salary caps, coaching personnel, and free agency. Inside Edge scouting service reports can even be acquired to give pitchers, fielders, or hitters an advantage when facing a particular athlete, from knowing a batter's weaknesses at the plate to learning what types of pitches to expect in specific situations. Player morale is also included, which can affect in-game performance. Key differences between the Wii game and other versions, other than the visuals, are the lack of playable minor league teams and online support. ~ Scott Alan Marriott, All Game Guide