Justin Edinburgh's side are now unbeaten in three league games after goals from Conor Washington, Andrew Hughes and Ismail Yakubu gave them their fifth home win of the season.
Washington opened the scoring for Newport in the 23rd minute when Southend goalkeeper Dan Bentley failed to clear Robbie Willmott's long ball and the striker raced through to tap into an empty net.
Southend equalised in the 41st minute when defender Ben Coker curled a superb free kick into the top corner from 20 yards.
The home side snatched back the lead in first half injury time though when substitute Hughes headed in off the post after Lee Minshull nodded Willmott's corner back across the box.
Yakubu then added a third goal seven minutes after the break when he met Washington's excellent cross from the left with a firm header.
Washington almost got a second soon after but his low shot came back off the post.