Second half goals from Nathan Tyson and Danny Senda gave Wycombe their fifth victory of the season.
Southend, who saw Mark Bentley put them in front, were by far the better side until the hour mark when the Choirboys clawed their way back into the match.
A quiet opening was punctuated after 11 minutes when Bentley's through ball was met by the onrushing Lewis Hunt but Frank Talia dived at his feet.
Wycombe's first chance came on 20 minutes when Adam Birchall capitalised on a Duncan Jupp mistake to cross to Tyson but his tame shot was cleared by Adam Barrett.
Southend upped the pressure with Tes Bramble pumping a low 25-yarder straight at Talia after 31 minutes.
Bentley then made a scorching run, turned Gus Uhlenbeek and fired in a vicious ball across the face of the goal just past the outstretched foot of Carl Pettefer.
Midfielder Bentley then set up Bramble, whose shot was spectacularly tipped wide by Talia.
The Shrimpers' pressure finally paid off after 42 minutes when Pettefer crossed from the right and Bentley headed home at the far post.
Southend looked the more dangerous side in the second half with Hunt, Mark Gower and Lawrie Dudfield all firing off target.
But the Chairboys equalised when Keith Ryan's clearance set Tyson clear. As home fans screamed for offside Tyson blasted the ball with his left foot past the onrushing Darryl Flahavan on the hour.
The goal lifted the visitors and on 65 minutes Tyson beat Barrett before unleashing another shot from 18 yards that Flahavan turned wide for a corner.
Pettefer rattled Talia's right post after 75 minutes but it was Senda who grabbed the winner with a rising 30-yard shot that went over Flahavan and into the top right corner seven minutes from time.