Woking failed to make much impact in the first half, although they did look dangerous on the break.
Steve Daly had the first chance of the evening as he looked to head the home team in front. Woking Goalkeeper Shwan Jalal was equal to it, gathering the ball just before the Southport striker made contact.
Southport opened the scoring on 22 minutes when Steve Pickford's corner was fed to Robbie Booth, whose shot was cleared to Liam Blakeman. The midfielder fired the ball into the back of the net from a tight angle on the right side of the 18-yard box, giving Jalal no chance.
Southport created various other chances to extend their lead, the best falling to Booth who turned well in the box just before the half-time break, but his fierce shot went straight into the arms of a grateful Jalal.
Woking had to wait unit the 53rd minute to have a shot on target, when Karl Murray tried his luck from 20 yards out, but his effort was comfortably collected by Steve Dickinson in the home goal.
Southport went in search of extending their lead, having two glorious chances within a couple of minutes just after the hour mark.
The first chance fell for Gary Brabin who headed a free-kick delivered by Pickford, but the ball was dramatically tipped over the bar by Jalal.
Moments later Blakeman fed a ball through to Daly, but he was well tackled by Tom Hutchinson just as he lined up a shot.
Southport held firm despite a barrage of late pressure from Woking to lift themselves off the bottom of the table.