Overcoming a slow start at Ikon Park on Sunday, the Lions lifted after quarter-time, kicking six of the next seven goals to win 9.2 (56) to 6.7 (43) and progress to a sixth-consecutive preliminary final.
Melbourne blew multiple opportunities to reduce the margin in the third quarter, before Ellie Hampson kicked a classy goal on the run right before the siren to extend the Lions' lead to a matchwinning 14 points.
Brisbane had contributors across the ground, while the Demons relied too heavily on superstar Kate Hore (31 possessions, eight clearances).
Melbourne's captain produced a stunning first quarter of 10 disposals, four clearances and 1.1 to inspire the Dees to a 14-point lead.
Hore brought up 100 career AFLW goals, becoming the second player to achieve the feat after Port Adelaide's Gemma Houghton managed it last week.
Star Lions midfielder Ally Anderson (28 disposals) was outstanding and kicked two last-quarter goals, while Belle Dawes was one of many Brisbane players to lift after a quiet start.
It is the Lions' first finals win against Melbourne after losing a preliminary final, then a grand final during the two seasons played in 2022.
Lions coach Craig Starcevich admitted the club used those defeats as motivation.
"That was front of mind, absolutely," he said.
"You want to make sure that you don't have that monkey on your back for too much longer."
Brisbane will have a week off before hosting a preliminary final against Carlton or Hawthorn.
Rampaging reigning premiers North Melbourne are in the other preliminary final after destroying the Hawks on Friday night for a record-extending 25th-straight win.
The Lions beat North to win the 2023 premiership, before the Kangaroos reversed the result last year for their first AFLW flag.
Melbourne suffered injury blows before and during the game.
After losing important defender Maeve Chaplin to a hamstring injury during the week, the Demons ruled out Eden Zanker after the forward suffered a head knock in the first quarter.
Melbourne coach Mick Stinear confirmed Zanker had been placed into concussion protocols and would miss the Demons' sudden-death semi-final against Adelaide next week.
Stinear also said Chaplin would be doubtful to return for the clash with the Crows but was progressing well from her injury.
"For us as a team, it's step up," Stinear said.
"Let's get after it together and keep the dream alive for players like Maeve and Edo (Zanker).
"But we've got a lot of depth ... six or seven players that missed out today that would have loved to have been out there."
Brisbane defender Jen Dunne was distraught when she came from the ground clutching her knee in the second term, but was able to return after receiving medical treatment.
Starcevich admitted he was a "little bit worried" and Dunne would have scans when she was back in Brisbane.
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