Chris Lever struck a last-gasp penalty to give Southport all three points against Ebbsfleet United.
The visitors missed a great chance to lead when Lever handled in the box, Liam Enver-Marum saw his penalty saved.
Southport then saw a spot-kick of their own saved as Preston Edwards denied Tony Gray after James Folkes fouled Shaun Whalley.
Patrick Ada was then sent off for fouling Chris Almond inside the box and Lever made no mistake from the spot.
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Ebbsfleet manager Liam Daish told BBC Radio Kent:
"Disappointing, the game hinged on a mistake, it's a long way to come for that.
"Looking at the second half performance we didn't do enough to win the game, we've got to wise up a bit in certain situations.
"Another missed penalty, you've got a penalty to go ahead and we don't score them, we've got to be more ruthless because opportunities don't keep showing themselves."