Themade the Final Four last year and earned a top seed by thrashing all comers in the Big East tournament.
But the Midwest Region is considered the toughest regional by far of this year's NCAA tournament, making a return trip to the Final Four anything but guaranteed.
College basketball betting begins in the Midwest Thursday with six "second-round" games in Auburn Hills, Lexington and San Jose.
Third-seededgets to start the tournament in its home state, as the Spartans play 14th-seeded at the Palace. Then sixth-seeded Memphis Tigers, the dual champion of Conference USA, takes on the winner of Tuesday's St. Mary's/Middle Tennessee game.
Fourth-seeded, the dual champion of the Atlantic 10 Conference, is rewarded for its efforts with a trip to San Jose to play 13th-seeded . Then fifth-seeded takes on the 12th-seeded , which won the Pac-12 Tournament.
And Louisville opens its NCAA tournament on the home court of hated rival Kentucky, Rupp Arena, by playing the winner of Tuesday's North Carolina A&T/Liberty game. Then eighth-seeded Colorado State, one of five Mountain West teams to make the tournament, matches up with ninth-seeded Missouri, one of just three SEC teams to make the Big Dance.
Then Friday in Philly, second-seeded Duke goes against 15th-seeded Albany, and seventh-seeded Creighton battles 10th-seeded Cincinnati.
In the early betting the Spartans were favored by 10 points over the Crusaders; the Billikens were favored by nine points over the Aggies; the Cowboys were favored by three points over the Ducks; Mizzou, despite being the lower seed, was favored by three points over CSU; the Dukies were favored by 17 points over the Great Danes; and the Blue Jays were favored by three points over the Bearcats.
On the college basketball futures market at Bovada.lv, Louisville was an even-money favorite to win the Midwest, followed by Duke at 7/2, Michigan State at 6/1, St. Louis at 8/1, Creighton, Oklahoma State and Missouri at 20/1, Memphis at 35/1, Colorado State, St. Mary's and Cincinnati at 50/1, Oregon at 60/1, Middle Tennessee at 75/1, Valpo at 100/1, New Mexico State at 200/1, Albany at 2000/1 and Liberty and NC A&T at 4000/1.