With the No. 1 overall seed in the tournament, Louisville is thus the favorite to succeed Kentucky as NCAA men's basketball champion.
Not only that, what the Cardinals hope will be their route to a national championship will start in the Midwest Regional on the home court of the archrival Wildcats, Rupp Arena.
UK, meanwhile, did not make the 68-team NCAA field.
U of L (29-5) lost to UK in last year's Final Four, 69-61.
On Saturday, though, the Cards won the Big East Tournament for the second year in a row by coming from 16 points behind to top Syracuse 78-61, their 10th consecutive victory this season. They will open NCAA play Thursday against Liberty or North Carolina A&T.
Big South tourney champion Liberty (15-20) and Mid-Eastern Athletic tourney winner A&T (19-16) will meet Tuesday at Dayton, Ohio.
"We are ecstatic to be the number one seed," Coach Rick Pitino said in a U of L press release, "particularly after finishing off one of the greatest conferences in the history of college basketball with a Big East championship. Our players showed incredible grit to come back from 16 points down.
"We know we will be challenged right away in one of the toughest brackets that I've seen in quite some time. I think our guys are up for the challenge. We look forward to it."
A win Thursday would advance the Cardinals to a Saturday matchup against the winner of Thursday's game between Colorado State (25-8) of the Mountain West and Missouri (23-10) of the Southeastern Conference, at-large picks and the 8-9 seeds in the region.
U of L beat Missouri 84-61 Nov. 23 in the Battle 4 Atlantis in the Bahamas.
This marks the third time Louisville has been seeded No. 1 in regional play and the second time the Cardinals have been the overall No. 1 pick. This is U of L's 39th NCAA appearance.
U of L was No. 1 in the 1983 Mideast Regional, advancing to the Final Four before falling 94-81 to Houston. To get to that game, Louisville won the "Dream Game" regional finals in overtime, 80-68 over UK.
The Cards were the overall No. 1 seed in 2009. They opened Midwest Region play with a 75-54 win over Morehead State, then beat Siena 79-72 and Arizona 103-64. The Cards fell in the Elite Eight, 64-52, against Michigan State.
The current Cardinals have the Big East tourney MVP in point guard Peyton Siva (10.0 ppg, 5.9 assists, 2.2 steals).
Siva is joined on the wings by Russ Smith (18.1 ppg, 3.6 rpg, 2.0 steals) and Wayne Blackshear (8.0 ppg, 3.2 rpg).
U of L starts Big East Defensive Player of the Year Gorgui Dieng (10.0 ppg, 9.9 rpg, 2.5 blocks) at center and Chane Behanan (9.9 ppg, 6.6 rpg) at power forward.
Louisville's calling card is a pressing defense that helped cause opponents an average of 18.7 turnovers a game.
The school said in a press release that ticket requests from fans exceeded U of L's allotment for Lexington. Season ticket-holders who requested tickets were to be contacted via email Sunday and notified if they were successful or not. Student ticket information will be distributed Monday via email.
Other tickets remain available via www.ncaa.com/mbbtickets or by calling 877-NCAA TIX (877-622-2849). Based on availability, all-session tickets will go on sale at the Rupp Arena box office starting Monday at 10 a.m.
Thursday's other games in Rupp Arena, from the East Region, will pit Butler against Bucknell and Marquette versus Davidson.
The other regional top seeds, in order, are: Kansas (29-5, South Region), Indiana (28-6, East) and Gonzaga (30-2, West).
THURSDAY Louisville vs. Liberty or North Carolina A&T
When: 6:50 p.m. (TBS)
Where: Rupp Arena
Records: Louisville 29-5; Liberty 15-20, North Carolina A&T 19-16
ABOUT N.C. A&T
Location: Greensboro, N.C.
School colors: Blue and gold
Head coach: Cy Alexander (19-16 in first season at North Carolina A&T; 363-325 in 23rd season overall)
Conference: Mid-Eastern Athletic
Last NCAA Tournament appearance: 1995
All-time NCAA Tournament record: 0-9
Series vs. Louisville: Louisville leads 1-0
Location: Lynchburg, Va.
School colors: Navy, white and red
Head coach: Dale Layer (63-67 in fourth season at Liberty; 166-173 in 11th season overall)
Conference: Big South
Last NCAA Tournament appearance: 2004
All-time NCAA Tournament record: 0-2
Series vs. Louisville: First meeting