In a game spoiled by swirling high winds, Stags went ahead through Sam Clucas and sealed the points courtesy of James Jennings' finish.
United ended a disappointing afternoon with 10 men after substitute Conor Clifford was sent off for showing his studs in a tackle on Matt Rhead, but Ryan Leonard grabbed a late consolation to ensure it finished 2-1.
The first half saw few chances in the wind, but the chances that were created all fell to Mansfield.
Shrimpers goalkeeper Daniel Bentley superbly parried Clucas' first-time finish from seven yards from a Darryl Westlake cross.
Rhead then shot straight at Bentley before Clucas broke through after 36 minutes.
Martin Riley hooked the ball upfield from his own half and Clucas outpaced two defenders to drill home low under the 'keeper from the left of the penalty area.
It took Southend 56 minutes to fashion a chance, Barry Corr dummying from a free-kick to allow Lee Barnard to send a low 12-yard shot wide.
Instead Stags doubled their lead after 65 minutes as Jennings rammed home from close range after Bentley could not hold on to a Rhead header from Chris Clements' corner.
Southend almost pulled one back as Clifford tried to lob Alan Marriott from 18 yards after the 'keeper had left his line to punch but saw his effort hit the crossbar.
United frustrations then boiled over nine minutes from time as Clifford dived into a tackle on Rhead for a straight red card.
Then in the last of five minutes of stoppage time, Corr struck the woodwork with a low shot and seconds later, from 18 yards, Leonard drilled across 'keeper Marriott and just inside a post.