The lively Lallana struck his 11th and 12th goals of the season either side of half-time to help Nigel Adkins’ side return to winning ways following their midweek draw with Ipswich.
Southampton had further opportunities to add gloss to the scoreline, with visiting goalkeeper Luke Steele denying Lallana his hat-trick and substitute David Connolly late on.
The win sees Saints move three points clear of second-placed West Ham, held 1-1 by relegation candidates Doncaster, and extended their unbeaten league run to nine matches.
Keith Hill’s struggling side were left to rue Stephen Foster’s first-half miss and, despite Danny Rose heading against the crossbar, they were condemned to a fifth straight away league defeat.
The visitors enjoyed a lively start with debutant Frank Nouble, who joined the Tykes on loan from West Ham this week, providing some teasing crosses but it was Saints who started to create chances.
Top-scorer Rickie Lambert had the first opportunity, striking an 18-yard effort straight at Steele, before Tadanari Lee failed to direct a header on target.
At the other end, Frazer Richardson’s tame backpass almost fell into the path of Craig Davies, while Barnsley could have levelled in the 18th minute but unmarked defender Foster glanced a header wide from David Cotterill’s inviting corner.
Daniel Fox, the only Saints change from the side that played the Tractor Boys, delivered a threatening free-kick, only for Jose Fonte to header just over the top.
On the half-hour mark, David Cotterill curled an excellent shot just wide of Kelvin Davis’ post before Saints broke the deadlock two minutes later through Lallana, who found the bottom corner from 18 yards after a Lambert knockdown.
And Lallana went in search of a second, firing just wide from 25 yards as Southampton finished the half strongly.
Southampton came out of the blocks strongly after the interval, with Morgan Schneiderlin stinging the palms of Steele from long range.
And Saints doubled their advantage after 53 minutes when Lee skipped past Scott Wiseman and, approaching the byline, slid the ball back for Lallana to tap in from close range.
Dangerman Lallana continued to torment Barnsley, bringing a comfortable save out of Steele with a 20-yard strike just after the hour mark.
Hill’s side almost pulled a goal back after 72 minutes when Rose headed Matty Done’s cross against the bar while, at the other end, Steele parried substitute Connolly’s close-range effort to safety.
Nouble and Davies fired over from distance as Barnsley tried to net a late consolation.