Starter Brandon Leibrandt was pulled after he recorded one out for the Seminoles, who used eight pitchers to tie a CWS record for a nine-inning game.
Robert Refsnyder and Bobby Brown homered in a span of three at-bats in the fourth as the Wildcats built their lead to 10-1.
Kurt Heyer (13-2) worked 7⅓ innings while taking the national lead for wins.
The Wildcats (46-17) won Bracket 1 and will open the best-of-three finals Sunday. Arizona will play for its fourth national championship, and first since 1986.
The Wildcats have won nine games in a row and are 56-0 when scoring nine or more runs since March 2010.
The Seminoles (50-17) were making their 21st appearance in Omaha and no other team has played in the CWS as many times without winning a championship.
Leibrandt (8-3) was knocked out after 4⅓ innings of the Seminoles’ 4-3, 12-inning loss to Arizona last Friday. On Thursday, he threw 31 pitches, only 15 strikes, and his throwing error set the stage for Arizona’s big first inning.
Leibrandt’s struggle marked the third time in this CWS that a starting pitcher lasted an inning or less. Florida’s Hudson Randall made it one inning against Kent State on Monday and UCLA’s Zack Weiss was pulled after one-third of an inning against Florida State on Tuesday.
Arizona’s six runs in the first resulted from four singles, three walks, a sacrifice fly and the three errors.
The Wildcats got their first extra-base hit of the CWS in the fourth when Refsnyder drilled a shot into the left-field bullpen for his seventh homer of the season. Seth Mejias-Brean followed with a double, and then Brown lofted a ball into the right-field bullpen for his fifth of the year.
Heyer scattered nine hits, walked three and struck out three. His 7⅓ innings raised his nation-leading total to 153, the most of any pitcher in Division I since 2006.