The second-seeded Lady Vols (26-7), who improved to 52-0 in NCAA tournament games on their home floor, will play Oklahoma on Sunday.
Tennessee is the only program to play in all 32 women's NCAA tournaments. The lone time the Lady Vols lost in the first or second round came when they fell 71-55 to Bowling Green in a 2009 opening-round game.
Alexis Akin-Otiko scored 12 points for No. 10 seed Creighton (25-8), which was denied its first appearance in a regional semifinal.
Tennessee led 35-31 early in the second half before a 13-0 run broke the game open. Creighton couldn't cut the margin below nine points the rest of the way.
The Lady Vols won by silencing Creighton's 3-point attack.
Creighton came in ranked second nationally with just over nine 3-pointers per game, but Tennessee outscored the Bluejays from beyond the arc. The Lady Vols were 6 of 10 from 3-point range, while the Bluejays went 4 of 22.
Ariel Massengale, Meighan Simmons and Taber Spani each went 2 of 3 from long range. Massengale scored 11 points for Tennessee, while Simmons and Spani each added 10.
Tennessee improved its all-time NCAA tournament record to 114-23, a mark that includes eight national titles and 18 Final Four appearances. Creighton is 3-5 in NCAA tournament games.
But neither Tennessee's partisan crowd nor the Lady Vols' rich postseason history intimidated Creighton in the early going.
Creighton briefly led 16-15 midway through a first half that also featured five ties, the last coming after Creighton center Alyssa Kamphaus made it 24-24 on a layup with 3:38 left. Tennessee led 35-29 at halftime.
Kamphaus, a 6-foot-3 junior, is Creighton's only player over 6 feet — Tennessee has six players taller than that — but the Bluejays finished the first half with just as many rebounds (16) as Tennessee and actually outrebounded the Lady Vols 9-7 on the offensive glass.
But the Bluejays couldn't maintain that momentum and missed 11 of their first 12 shots in the second half.
After McKenzie Fujan's basket cut Tennessee's lead to 35-31 with 17-35 remaining, Tennessee turned up its defensive intensity and broke the game open.
Spani started the run with a 3-pointer and followed with a steal. Bashaara Graves delivered a basket in the paint. Williams then made a steal and passed to Simmons, who threw it back to Simmons for a fast-break layup. Massengale and Simmons capped the 13-0 spurt by sinking consecutive 3-pointers.
Tennessee eventually led by as many as 19. Creighton got back into the game with a 7-0 run, cutting the deficit to 59-50 on a pair of Ally Jensen free throws with 4:42 left, but that's as close as the Bluejays got the rest of the way.