Scarborough Athletic's FA Cup adventure came to a halt after a 5-2 defeat on the road at Southport
John Deacey's men started brightly and had the first effort on goal, James Walshaw rifling into the side-netting, although the lineman's flag was raised anyway.
Southport fired back and Tommy Taylor was forced into a smart stop down to his left before the follow-up effort was drilled wide.
It was the visitors who took the lead though, Walshaw angling a drive across Charles Albinson in the Southport goal and into the bottom corner.
Boro's lead didn't last long however as Reagan Ogle's long throw-in was directed past Taylor at the near post by Jack Sampson for 1-1.
The hosts spurned a couple of half-chances to take the lead for the first time in the contest before a searching pass from Wayne Brooksby found Michael Coulson, but Albinson did well to deny him.
Boro were dealt a blow on 22 minutes when Chris Howarth limped off and was replaced by T'Nique Fishley.
Taylor then had to be alert again when David Morgan released Kieran Glynn, the Boro stopper denying him with an impressive stop.
Ogle's long throw-in worked again for hosts Southport on 38 minutes when Zehn Mohammed was on hand to fire them 2-1 up heading into the interval.
That lead was soon extended after the interval, Sampson bagging his second after smart work from Raul Correia in the build up.
The game was put to bed when the hosts helped themselves to a third goal from Ogle's long throw, Sampson applying the finishing touch for 4-1 and his hat-trick.
Taylor was once again called upon to keep Southport at bay, first denying Morgan before a smart stop to prevent Correia applying the finishing touches to another raid from the hosts.
Luke Lofts dragged an effort wide after patient approach play from Boro, but they soon fell further behind.
Debutant George Newell, brought on in place of hat-trick hero Sampson, slotted in a fifth for Southport to make it 5-1 after being played in by Connor Woods, who had also been introduced from the bench.
Youngster Kian Spence was brought on for Ryan Watson on 74 minutes and two minutes later Boro notched a consolation goal, skipper Coulson scoring from the penalty spot.
Sub Spence had a couple of pops at the Southport goal, but his efforts were wayward and drifted off target to wrap up a disappointing afternoon for Deacey's men.
Boro are back in league action on Tuesday evening when they make the trip to Radcliffe Borough.
BORO: Taylor, Howarth, Brooksby, Watson, Lowe, Assenso, Johnson, Lofts, Walshaw, Walker, Coulson (c). Subs: Spence( on for Watson 74), Morgan (gk), Fishley (on for Howarth 22), Annan, Davidson, Dawson, Merris