Saints' first game of the Ronald Koeman era ended in a narrow defeat as they were beaten 2-1 by Liverpool at Anfield.
Reds striker Daniel Sturridge shouldered the responsibility as Liverpool's new main man up front with a late winner.
With last season's 31-goal star Luis Suarez having departed to Barcelona for £75m there is a shortfall to be accounted for - but Sturridge and the Reds' other scorer Raheem Sterling showed they are up for the challenge.
Such was Suarez's brilliance it is almost forgotten Sturridge was the Premier League's second highest scorer with 24 last season - but without his world-class partner beside him there is a greater burden on him to deliver.
With the England striker having a relatively quiet 80 minutes it seemed Saints would leave Anfield with at least a point after Nathaniel Clyne's second-half equaliser, only for the 24-year-old to pounce on his first clear-cut chance.
There had been significant change for both sides over the summer. Liverpool spent upwards of £100m on eight new signings, while their opponents were still in debit having seen a raft of departures - three players to Anfield and manager Mauricio Pochettino to Tottenham.
Only five of Saints' starting line-up started their final match of last season, with four players making their debuts and new £12m striker Shane Long on the bench.
The most significant absenteefor Liverpool, however, was Suarez. However, a year ago Liverpool began the season without the suspended Uruguayan and took 10 points from their first four matches.
While a suitable replacement up front still remains a target for Brendan Rodgers, arguably his most important summer signing was that of Dejan Lovren - who made his debut against the club he left acrimoniously, albeit for £20m.
Liverpool are still looking for a leader in defence to fill the void left by Jamie Carragher's retirement the year before last and the manager's hope is the Croatian fits the bill as it was an area of weakness which cost them valuable points in their surprise title challenge last season.
The centre-back, incessantly booed by the visiting fans, certainly added more of a presence alongside Martin Skrtel and won headers in situations which have often caused problems in the past.
It was not all plain sailing at the back in the first half with goalkeeper Simon Mignolet getting in a tangle with Graziano Pelle at Southampton's first corner and almost presenting the visitors with an easy chance.
But Liverpool's strength remains in the final third of the field and after scoring 101 goals last season, Sterling opened their account in an incisive attack which split Southampton wide open.
Midfielder Jordan Henderson won the ball in a tackle with Morgan Schneiderlin 10 yards inside his own half and produced a great through-ball for Sterling, who rushed through and shot past Fraser Forster, making his debut following a £10m move from Celtic.
Forster got closer to Sterling's snap-shot on the stroke of half-time and parried - but it was his Liverpool counterpart who produced the better saves of the first half as he clawed away a James Ward-Prowse inswinging free-kick and tipped over a Schneiderlin effort.
However, 10 minutes after the break he could do nothing with Clyne's powerful drive after the Saints full-back continued his run off the right flank to collect a Dusan Tadic backheel which beat Lovren.
Mignolet kept out Davis minutes later with a low save after the midfielder found himself unmarked free 12 yards out as Southampton stepped up the pressure, while another surging Clyne run was halted only by a desperate Glen Johnson tackle.
England striker Rickie Lambert, another Liverpool acquisition from Southampton, came off the bench and had a chance to score with his second touch before Sturridge grabbed the winner with 10 minutes remaining.
Henderson's cross was half-cleared by Victor Wanyama and Sterling nodded it back into the danger area, where his England team-mate poked home from close range.
But Liverpool were ultimately indebted to Mignolet, who in the opening game 12 months ago saved a last-minute penalty to secure victory.
This time he brilliantly tipped Schneiderlin's shot onto the bar in the 88th minute - and watched relieved as Long headed the rebound wide from six yards out.