A 14th minute penalty from Freddy Eastwood, who has been the Shrimpers' top scorer for the last two seasons, settled the issue at a boiling hot Roots Hall.
Stoke made a promising start when Carl Hoefkens' throw in was headed on by Southend centre-back Adam Barrett into the path of winger Peter Sweeney, whose header forced a one-handed save out of keeper Darryl Flahavan.
Summer signing Vincent Pericard saw his follow-up shot turned out for a corner by Blues centre back Spencer Prior.
The Shrimpers kept conceding possession but while City passed the ball around neatly it was the League One champions who looked sharper in attack.
One such foray resulted in the opening goal as Adam Barrett's throughball released forward Lee Bradbury.
His charge ended when goalkeeper Steve Simonsen raced out and brought the forward down. Referee Mike Russell pointed straight at the spot and Eastwood fired low to his right to send the custodian the wrong way.
The Potters replied with Mali international Mamady Sidibe heading Sweeney's corner over the bar before Southend created a string of opportunities to extend their lead.
Mark Gower had a goalbound header deflected out for a corner before Eastwood's dipping 20-yard shot was inches over the crossbar.
Then Eastwood fed Luke Guttridge whose shot forced a save from Simonsen.
And on the half-hour mark Stoke nearly grabbed an equaliser when the ball bounced off Prior into Pericard's path but Flahavan saved and then gathered the rebound.
The Potters started the second half brighter with Sidebe's 10-yard shot blocked by right-back Simon Francis.
Sidibe then turned provider two minutes later to set up a Pericard effort that was blocked by centre back Barrett.
Southend responded with Eastwood hitting a 25-yard effort over the bar before the striker latched onto a Gower pass to force a good parry from Simonsen which went out for a corner.
But it was the Stoke fans that were left gasping when Hannes Sigurdsson – a substitute for winger Luke Chadwick, who was stretchered off wearing an oxygen mask – rifled in a 30-yard shot that Flahavan dived to save.
Yet Southend came closest to adding to their advantage two minutes from time when Eastwood beat summer recruit Danny Higginbotham to set up substitute Lewis Hunt, who six-yard shot was beaten by a reflex save from Simonsen.