The O's, who had parted company with manager Martin Ling on Sunday, looked set for a victory that would have lifted them out of the bottom four after Adam Boyd opened the scoring on 11 minutes.
But caretaker boss Kevin Nugent's hopes of starting with a win were cruelly wrecked by Walker's last-gasp strike.
In a frenetic derby duel, the game was only 11 minutes old when Adam Chambers saw his pass deflected by Johnny Herd and it fell neatly into the path of top scorer Boyd, who slotted home for his ninth league goal of the season.
Southend were forced into an early change when veteran striker Dougie Freedman was replaced by Lee Barnard, but it was the home side who continued to press.
Boyd saw a snapshot tipped away by Steve Mildenhall in the visiting goal, while Harry Baker, who was making his full league debut, twice went close.
Southend almost levelled just before the break when home keeper Glenn Morris blasted a clearance against Alex Revell but the ball rebounded just wide of the post.
After the interval, the dangerous Kevin Betsy shot across the face of the Orient goal, while at the other end Boyd had a shot tipped away.
Orient were hanging on in the closing stages but when Jean-Francois Christophe had a goal disallowed four minutes into stoppage time, they looked to be on their way to their first win in nine games.
But there was still time for a sting in the tail when Walker, who had previously been on loan at Orient, raced down the left, cut in and fired a fierce shot from 18 yards that exploded into the net.