Freddy Eastwood scored his 50th goal for Southend, and it was enough to give them a winning return to the Championship at Stoke's expense.
The sought-after forward slotted home a 14th-minute penalty after Lee Bradbury was fouled by keeper Steve Simonsen.
Early on, Darryl Flahavan made saves from Peter Sweeney and Mamady Sidibe's follow-up, while a stunning save from Simonsen denied Lewis Hunt later on.
On the hour, Luke Chadwick was carried off, seemingly wearing an oxygen mask.
Southend boss Steve Tilson on the future of star striker Eastwood:
"Freddy can score at any level.
"If he has scored 10 or 15 goals by Christmas, then Premiership clubs will be knocking on the door.
"Freddy is happy here, and the club do not want to sell him - which is good news for me. He can get even better."
Stoke boss Tony Pulis on Luke Chadwick, who was taken to hospital:
"Luke was unconscious, and he was still in that state when they were taking him to hospital.
"They revived him on the pitch, but he fell unconscious again. I don't know what led to it but it's a huge concern.
"We had enough chances to win the game, and I can't fault the players effort."
Southend: Flahavan, Francis, Prior, Barrett, Hammell, Campbell-Ryce (Paynter 71), Maher, Guttridge (Clarke 90), Gower (Hunt 86), Bradbury, Eastwood.
Subs Not Used: Collis, Lawson.
Goals: Eastwood 14 pen.
Stoke: Simonsen, Hoefkens, Duberry, Hill, Higginbotham, Chadwick (Sigurdsson 61), Brammer, Russell, Sweeney (Eustace 68), Sidibe, Pericard.
Subs Not Used: Duggan, Pulis, Dickinson.
Ref: M Russell (Hertfordshire).