Jack Hobbs' own goal and a second half Jos Hooiveld effort proved the difference at the KC Stadium as the Championship leaders made the most of promotion rivals Reading and West Ham squandering points.
While Southampton are now unbeaten in 11 league matches, it was a predictably tight encounter between the second tier's tightest defence and top scorers.
Hull came into the match on an 11-game unbeaten run of their own, but that looked under threat from the outset.
Having made two impressive early saves, Vito Mannone had to pick the ball out of his own net after just 14 minutes when Hobbs directed a Danny Fox cross into his own goal.
Adam Lallana wasted a good chance to extend Saints' advantage moments later, before Josh King hit the bar at the other end and Robbie Brady fired over with the goal gaping.
Hull were made to pay for their wastefulness in the 59th minute when Jose Fonte crossed for fellow centre-back Jos Hooiveld to net his sixth goal of the season and wrap up victory.
It was Southampton that started the brightest at the KC Stadium, with Rickie Lambert forcing Mannone into action after eight minutes.
The Hull goalkeeper stopped the striker's header with ease and was forced into action again moments later to prevent a Lallana effort sneaking home.
King forced Davis into a superb one-handed save as Hull voyaged forward, although they were soon picking the ball out of their own net.
Left-back Fox fired a low driven ball across the six-yard box and Hobbs turned into his own net under pressure from Lambert.
Moments later Southampton should have doubled their advantage, although Lallana was guilty of fluffing his lines after rounding Mannone.
The chances seemed to spark Hull into life as they dominated proceedings for the remainder of the first period.
Manchester United loanee King hit the crossbar with a well-struck half-volley in the 25th minute, before Hobbs missed the chance to make amends for his earlier mishap by heading wide from a corner.
City continued to press for a leveller that should have come in the 35th minute through Brady, who somehow blazed over when it looked easier to score from a nicely-weighted King cross.
The Tigers again came close as half-time approached after slight hesitancy at the back, but Fonte redeemed himself to block a Robert Koren effort.
Hull boss Nick Barmby replaced the former Slovenia international with Aaron Mclean in a bid to freshen up his attack.
The alteration failed to bring about the change City had hoped for, though, as Southampton's centre-backs conjured up their second goal of the evening in the 59th minute.
Fonte found himself in an unusually attacking position on the right flank and delivered a cross that defensive partner Hooiveld converted from close range.
There was a rather subdued atmosphere in the KC Stadium as Hull struggled to penetrate the visitors' defence.
Barmby's man rallied in the final 10 minutes - with Davis producing superb saves to thwart King, Tom Cairney and Cameron Stewart - but Southampton did enough to hold out for three points.