The Iron have frequently been a thorn in the Shrimpers' side, but they lacked a killer instinct in front of goal as the hosts recorded their second 3-0 victory on the trot courtesy of goals from Freddy Eastwood, Lee Bradbury and Shaun Goater.
Scunthorpe created an early chance after six minutes when Andy Keogh got a touch to Ian Baraclough's corner, but the ball went harmlessly wide.
A minute later the Iron were left rueing that missed chance when Eastwood put the League One leaders ahead.
Luke Guttridge half volleyed a Scunthorpe clearance to Goater and he squared to Eastwood, who rifled the ball past a diving Paul Musselwhite from 20 yards.
The visitors replied with a low 30-yard Baraclough effort that Darryl Flahavan easily held before the Shrimpers threatened to double their advantage as Musselwhite was forced into action to deny Kevin Maher and Che Wilson.
Scunthorpe weathered that storm and then enjoyed long spells of possession, but they missed injured 20-goal top scorer Billy Sharp as the only test for Flahavan was a tame Keogh shot from just inside the box.
The second half started with Matt Sparrow firing over for the visitors, but they were punished for not creating better chances when Bradbury got his first goal for the Shrimpers since signing for the remainder of the season from Oxford.
Efe Sodje met Maher's free-kick at the far post and headed back across the six-yard box for Bradbury to tap home.
Flahavan dived to save a 35-yard Baraclough effort on 73 minutes but 120 seconds later Southend got their third.
There were calls of offside from the Scunthorpe defence as Mark Gower charged to the byline, but with no flag being shown he crossed to Goater, who turned and fired home into the left hand corner of the goal.