The Cardinals (30-9) coming off back-to-back losses at St. John's over the weekend will start Kyle McGrath (5-0) against the Commodores.
The game is slated for 6:30 p.m. at Jim Patterson Stadium and will be televised on the CBS Sports Network.
The winner of the Battle of the Barrel will take home the traveling trophy between the two schools.
U of L coach Dan McDonnell said the rivalry has become "a very good one, a nice border battle," between the two schools.
Vandy is 35-6 on the season and Walker Buehler (2-1, 2.76) will get the start for the Commodores.
Vanderbilt enters the game with 93 steals to rank ninth in the country and the Cardinals have 102 stolen bases to rank fifth.
Admission is free.