A tactical half-time change paid dividends for Exeter, as three goals early in the second half placed them in a dominant position, leaving Southport to rue chances missed in the first half.
Manager Alex Inglethorpe reverted to a 3-4-3 formation in the second half which outwitted Southport. Dominic Krief's goalmouth mis-kick was just too good an opportunity for Craig Farrell who slotted the loose ball home from close range.
As Southport pressed for an equaliser, they were left short at the back allowing Farrell to feed the ball to Lee Phillips whose shot fired off Steve Dickinson ending up in the back of the net.
Minutes later, Southport fell further behind when Farrell secured his second of the afternoon when he received the ball from Phillips, drilling the ball home from 20 yards.
All this undid Southport's dominance of the first half with Steve Daly, Terry Fearns, Carl Baker and Steve Pickford all having real chances to score, with Exeter looking careless and finding it difficult to gain control.
Indeed, Exeter failed to create any clear cut first-half chances, as the home side dominated proceedings.
Southport were deflated and unable to respond, finding themselves switching attention to Tuesday night's fixture, as Exeter defended resolutely, riding out their victory, embedding themselves at the top of the Conference table.