Crewe carried a 1-0 lead into the match at Roots Hall from Saturday's first leg and moved ahead when Ajay Leitch-Smith slammed a blistering shot into the corner of the net from inside the box on 24 minutes to give his side a 2-0 aggregate advantage.
Southend equalised on 64 minutes when substitute Neil Harris scored from close range after Steve Phillips had somehow spilled Chris Barker's cross.
Paul Sturrock's side were well on top having saw Michael Timlin and Freddy Eastwood hit either visiting post at the outset of the second period, but they were undone when Crewe caught them on the break as teenage substitute Max Clayton slipped the ball home for a second goal on 86 minutes.
Southend kept their hopes alive when Barker - making his 100th appearance for the home team - nodded in from Ryan Hall's cross a minute later, but they could not find an equaliser despite the best efforts of Mohsni Bilel who produced an outstanding effort in winning almost every ball up front with his head in the second period.
Crewe return to a Wembley play-off final for the first time since 1997.
They will face Torquay United or Cheltenham on May 27 with a place in League One up for grabs. Cheltenham hold a 2-0 lead from the first leg on Sunday before they play to a finish on Thursday evening.
Steve Davis's young Crewe side were made to sweat when they should have put the match to bed before half-time.
Byron Moore somehow lifted a shot over the bar from 15 yards out with just Cameron Belford to beat after the home goalkeeper had knocked the ball straight to him on 32 minutes.
Leitch-Smith should have added his second goal of the night three minutes before the break with just the keeper to beat, but he lobbed the ball straight into arms of Belford.
The second half saw Mohsni head straight at Phillips when he could have equalised on the night with five minutes left in a move that illustrated what might have been for a home team who must regroup for another season in League Two.
Southend have spent two seasons in League Two, and missed out on automatic promotion by one place and one point. Between September and March they were permanently in the top three. It was a tough loss to take.