Southampton had the game's first chance when they shot narrowly over the bar, but Liverpool soon began to take charge of the tie. Paul Anderson, who named among the subsitutes for the first team against Benfica, played in Craig Lindfield but his shot was blocked.
This was a momentary respite for the Saints before the Reds took the lead in the sixth minute. Adam Hammill won a free kick on the left which he took himself. His cross found reserve captain Jack Hobbs who cooly flicked the ball into the top corner to put Liverpool 1-0 up.
Liverpool doubled their lead seven minutes later when Craig Lindfield slid in on to a Charlie Barnett cross to convert what would be the game's winner.
Lindfield almost added a third in the 35th minute when he connected with a Paul Anderson cross but unfortunately the ball ended up on the wrong side of the post.
Liverpool were on top throughout but in the second half Southampton began to show the form that has got them this far in the competition. They pulled one back on 54 minutes and almost got an equaliser on the hour mark but were denied by some good goalkeeping from David Roberts.
Both sides continued to have chances but there were no more goals, leaving things finely poised when the Reds travel to Southampton for the second leg in a week's time.