The Atlantic Sun Conference tournament champion Buccaneers (36-22) open against regional host Vanderbilt (51-9) at Hawkins Field in Nashville. First pitch is set for 7 p.m. Eastern and the game will be shown on ESPNU.
The Commodores, who were seeded No. 1 in the Southeastern Conference tournament after winning the regular-season title, fell to LSU 5-4 in 11 innings on Sunday in the league's championship game.
"Vanderbilt is a tremendous ball club and we are going to be playing one of the top teams in the country," ETSU coach Tony Skole said in a statement from the university. "This will be a tremendous test for our guys, but the good thing is we have been to Nashville before.
"Vanderbilt has a handful of major leaguers on its team, but we won't be intimidated going into the regional. We have a tough group of players and have great leadership starting with our senior class. Our seniors have stepped up their play over the last month of the season and it was gratifying to see them win the championship on Sunday."
The Bucs and 'Dores are joined in the regional by Illinois (34-18) and Georgia Tech (34-25), which open play at 2 p.m. on Friday. The winner of the Vanderbilt Regional faces the Louisville Regional winner in the super regionals June 7-10.
Vandy is one of nine SEC teams in the 64-team NCAA field. The Yellow Jackets are one of eight Atlantic Coast Conference squads in the field, including No. 1 overall seed North Carolina.
Sixteen four-team, double-elimination regionals begin Friday. Best-of-three super regionals will be held next week, with those winners moving to the College World Series in Omaha, Neb.