Fit-again midfielder Jimmy Ryan had instant impact, setting up Ash Hunter to lob in the opener early on.
Within minutes it was 2-0, with Bobby Grant nodding home Antoni Sarcevic's cross from the left.
In the second half, Scunthorpe's Paddy Madden scored from the spot when Tom Hooper was pushed over, but Fleetwood ended strongly for a deserved win.
Scunthorpe caretaker boss Nick Daws told BBC Radio Humberside:
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"I think the performance was probably a bit chalk and cheese in terms of the two halves of the game.
"Everybody knows that getting the first goal is key, we didn't get that.
"We expected a really tough challenge after a really long week and successful week for us, but they got the first goal.
"Two things in the first half put us on the back foot, but we adjusted the shape slightly to stay in the game - I thought we did that really well and that was the foundation for our second-half performance which was excellent."

Margaret Stewart admitted stealing from her employer Ivanhoe Cambridge, which used to own Glasgow's St Enoch Centre.
She then used her position as treasurer at the boys club to pay cheques into its account before taking the cash.
At Glasgow Sheriff Court, Stewart, 48, from Hamilton, South Lanarkshire, was also told to repay £27,000.
The court previously heard that Stewart worked in the accounts department of Ivanhoe Cambridge UK, which sold the St Enoch Centre in 2013.
Between May 2008 and January 2011 she had managers at the firm sign cheques that were supposed to be used to make legitimate payments.
Stewart would then write over the payee name and insert the football team's name.
The money would go to the club before Stewart took it for herself.
She was caught after a bank spotted a problem with one of the cheques from Ivanhoe Cambridge and phoned her office.
Stewart then immediately confessed to her superiors and a payment plan was put in place for her to repay the money.
The court heard that although more than £5,000 was repaid, the plan was not completed and her house was put on the market.
The house was rendered worthless due to Japanese Knotweed, and Stewart was later reported to police.
Stewart appeared for sentencing on Thursday having earlier pleaded guilty to a charge of embezzling the money.
The court heard that Stewart's husband had been jailed in 2003 for three-and-a-half years for drug dealing and she had resorted to theft to repay the debts that he wracked up.
Imposing a community payback order, Sheriff Linda Ruxton told Stewart that her embezzlement was "deliberate and systematic" but she accepted the "impact on her of her husband's criminal behaviour".
The Rangers Supporters' Association Boys Club was founded in 1960 for boys between five and 17-years-old.
Former players include Barry Ferguson, Lee McCulloch, Graham Dorrans and Charlie Miller.

This is the new Virtual Reality (VR) version of Google Earth, as seen through the HTC Vive headset.
The way the HTC Vive's works means that as well as moving your head around to get different views, you can walk around your surroundings, try to see into Buckingham Palace or fly up to the top of the Eiffel Tower.
But while Google Earth's coverage of many of the Earth's cities and famous landmarks look great in VR, if you just wanted to explore your street, the VR experience might not be so good... yet...
The HTC VIVE is one of the latest VR headsets on the market, and we asked Newsrounders to check some of them out.
Virtual reality is still pretty new, and scientists aren't sure how it will affect people's health in the long-term, especially eyesight.
So most VR makers have guidelines which recommend that only people over the age of 13 play them.
Some people have also reported feeling a bit seasick whilst playing on them.
Fleetwood boosted their survival hopes by beating Scunthorpe for just their second League One win of the year.
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A woman who tried to launder £55,000 of stolen cash through Rangers Supporters' Association Boys Club has been told to carry out 260 hours unpaid work.
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Check out these superhero-eye views of cities around the world!