The winger, who left Roots Hall to join Barnsley in the summer in a £175,000 deal, created a goal out of nothing in the 22nd minute.
With his back to goal on the left, Campbell-Ryce turned Lewis Hunt and unleashed a rising shot from just outside the box that beat Darryl Flahavan at his far post.
Both sides played some neat passing football in the first half but, the goal apart, goalscoring chances were at a premium.
However, Southend were left wondering how they did not get something out of the game after forcing a string of good save out of Tykes keeper Heinz Muller.
The German saved a 30-yard Simon Francis effort in the first half and then weathered a storm after the break as Southend dominated possession.
Muller parried Tommy Black's snapshot before turning over another effort from the makeshift striker and saving debutant forward Lee Barnard's header from the resulting corner.
Muller also tidied up when Southend threatened in the box and he was ably assisted by central defenders Dennis Souza and Steve Foster, who both had fine games.
Tykes skipper Brian Howard came closest to doubling Barnsley's lead with a shot that went just over from 25 yards out late in the match.
The win was Barnsley's first away from Oakwell since they beat Southampton on September 22 and it confirmed the Tykes' first appearance in the fifth round since 1999.