The strike midway after 76 minutes condemned Peterborough to defeat following their promotion, in a match watched by manager Darren Ferguson's father, Sir Alex.
The Posh enjoyed pressed Blues back into their own half for much of the opening exchanges, but had little to show for it other than an off-target 12-yard shot from Aaron McLean.
Southend weathered the early storm and started to test the Peterborough defence. Posh left-back Russell Martin, making his debut, got a foot to Dan Harding's cross-field ball, but could not stop Damian Scannell unleashing a curling right-foot shot that went just wide of the post.
Transfer-listed Shrimpers midfielder Nicky Bailey, the subject of a rejected bid from Charlton Athletic, then rifled in a 30-yard effort that Joe Lewis held low down.
The Posh then blew a great chance to take the lead when winger Chris Whelpdale's centre from the right byline flashed across the face of goal and beyond the outstretched leg of Craig Mackail-Smith.
And the League One newcomers, who finished second in League Two last season, had the final say of the half when central midfielder Charlie Lee rifled a well-struck 25-yard shot just wide of a diving Steve Mildenhall.
The second half was a fairly scrappy affair until Clarke's goal, with both sides struggling to create decent chances.
Southend skipper Adam Barrett headed straight at Lewis from six yards, before a Bailey shot from a Franck Moussa lay-off was deflected just wide.
McLean had a great chance for the Posh but his shot from 14 yards was parried for a corner by Mildenhall.
Southend then upped the pressure and were nearly rewarded when Paul Furlong's header from a Bailey upfield ball was deflected on to the roof of the net by Peterborough skipper Craig Morgan.
Two minutes later last year's League One play-off semi-finalists made the breakthrough.
Debutant Dan Harding's corner from the right dropped to Clarke and he lashed it into the roof of the net from six yards.