The absence of injured striker Simeon Jackson was keenly felt by Gillingham as they slipped to a hefty defeat at St Mary's Stadium.
Dennis Oli moved into a lone forward role while youngster Luke Rooney made his first League start on the right side of midfield.
The Saints went on the attack direct from the kick-off and twice went close in the third minute, first Lallana testing Royce with a 20 yard drive before Jaidi headed wide at the far post from the resulting corner.
Moments later Gillingham were forced to make an early change as Danny Jackman exited clutching his shoulder to be replaced young Jack Payne.
Just as the visitors seemed to be silencing the home support Southampton scored, Dean Hammond crossing from the right in the 13th minute for Rickie Lambert to head into Royce's bottom left corner.
After that setback, the Gills slowly began to assert themselves on the game and equalised in the 26th minute in spectacular fashion. Curtis Weston holding the ball on the left side of the Saints area before laying off for Luke
Rooney to curl a 20 yard chip over Kelvin Davis and into the far corner.
The home side gave the visitors a scare in the 33rd minute as Southampton looked to regain the lead. Jacob Mellis striking the woodwork with a low effort from just inside the box. Seconds later they found the net through Papa Waigo N'Diaye who collected a neat flick on and beat Royce at his near post.
On the stroke of half time things got worse for the Gills as Mellis played a clever ball into the box for Adam Lallana to give the home side a 3-1 half time lead.
Gillingham's first opening of the second half came on 53 minutes as Andy Barcham tried his luck from outside the area but his rising drive failed to trouble keeper Davis.
On the hour mark Neal Trotman headed narrowly wide from Wotton's free-kick as the visitor's struggled to make any impact on the second half.
Southampton continued to look comfortable and were unlucky not to add to their tally in the 66th minute. Rickie Lambert curled a ferocious free-kick toward the top right corner of Royce's net but the experienced stop dived acrobatically to push it behind for a corner.
Another chance went begging for the home side on 71 minutes as N'Diaye broke into the Gills box and played an inviting ball across the face of goal but Wotton couldn't find the finish that the move deserved.
Seconds after the introduction of Mark McCammon, the Gills conceded their fourth of the afternoon, Adam Lallana finding acres of space on the left of the box to tuck a low strike into the far corner.
Attendance: 19457 (1961 Gillingham)
Gillingham: Simon Royce, Barry Fuller, Josh Gowling, Mark Bentley, Chris Palmer, Luke Rooney (Mark McCammon 73), Curtis Weston, Kevin Maher, Danny Jackman (Jack Payne 6), Andy Barcham, Dennis Oli.
Subs not used: John Nutter, Garry Richards, Jacob Erskine, Alan Julian, Rashid Yussuff.
Southampton: Kelvin Davis, Lloyd James, Radhi Jaidi, Neal Trotman, Dan Harding, Paul Wotton, Dean Hammond, Jacob Mellis, Papa Waigo N'Diaye (Lee Holmes 87), Adam Lallana (Simon Gillett 78), Rickie Lambert (Matt Paterson 88).
Subs not used: Tommy Forecast, Marek Saganowski, Chris Perry, Garyn Preen.