Substitute Jack Redshaw was the hosts' matchwinner courtesy of a superb finish with his first touch of the ball after 70 minutes.
The goal came within seconds of Southend wasting a glorious chance at the other end, allowing the Shrimps to break through right-back Shaun Beeley, whose cross was expertly finished by Redshaw.
Southend went close to a late equaliser, with Barry Corr heading over from six yards out and Conor Clifford shooting just over.
Morecambe started brightly as Andy Fleming and Kevin Ellison both drilled shots wide of the target in the first few minutes but it was the home side who struck first.
Former Morecambe winger Kevan Hurst delivered an inviting cross from the left and midfielder Ryan Leonard ran on to the ball perfectly and headed into the top corner.
Hurst himself went close to a second with a curling effort which flew just past a post before Morecambe levelled after 29 minutes through Ellison.
There looked to be little danger as the ball was pumped into the Southend area but a mix-up in the visitors' defence allowed the veteran striker the chance to slot the ball past Daniel Bentley from the tightest of angles by the left-hand touchline.