Scunthorpe were beaten 2-0 at Hartlepool United at Victoria Park on Saturday.
Jonathan Franks gave the hosts the lead midway through the first half and, though Scunthorpe pressed, the away side never really tested the home goalkeeper.
Josh Walker was sent off for handling on the goal-line late in the second period before Sam Slocombe saved the subsequent penalty from Steve Howard.
However, the scoring was completed by substitute Luke James five minutes from time, who scored with a sweet volley.
David Prutton came in for his first start to replace Robbie Gibbons in the starting eleven.
Slocombe started in goal, with Christian Ribeiro, David Mirfin, Niall Canavan and Tom Newey forming the defence.
The midfield consisted of Mark Duffy, Jimmy Ryan, Prutton, Walker and Andy Barcham, while Mike Grella started up front.
The substitutes were James Severn, Connor Jennings, Gibbons, Mark Hughes, Callum Howe and Jordan Keegan.
The opening opportunity of the game came the hosts' way on three minutes after Evan Horwood's curling free-kick beat Slocombe at his bottom left-hand post but drifted just wide.
The first Scunthorpe half-chance arrived five minutes later as Prutton played the ball into Grella, who teed up for Barcham, whose low half-volley went wide.
In the 13th minute, Prutton was again involved in the action, clipping a clever throughball to Grella who, under pressure from a defender, turned to strike a right-footed effort across but wide of Scott Flinders.
The away side's pressure continued, with Ryan and Duffy linking up before Ribeiro was played in and his low right-wing cross was blocked away for a corner in the 17th minute.
The next chance of the game came Hartlepool's way in the 21st minute as Anthony Sweeney's swing of the right boot resulted in his effort clearing the crossbar.
The hosts took the lead just two minutes later though as Andy Monkhouse's cross from the left wing evaded the away defence and found Jonathan Franks on the right side of the penalty area, who slotted home on the half-volley.
After the goal, Scunthorpe tried to find their way back into the game, but the match had entered a scrappy lull with both sides losing possession too easily.
In the 39th minute, the Iron hit the woodwork as Canavan's volleyed effort after Walker's corner had only been part cleared, bobbled onto the crossbar and bounced back out of play.
As the half drew to a close, Scunthorpe were enjoying a good spell of possession, but it was the hosts who had the last opportunity of the opening period, as James Poole curled an effort wide of goal after being played in down the left side pf the area.
Scunthorpe next came close five minutes into the second period when Walker fizzed an effort over the crossbar after good work by Ribeiro and Duffy out wide on the right.
Then, a minute later, Poole chested the ball down and got it under control for the hosts before sending a speculative volley towards Slocombe, which the shotstopper saved comfortably.
In the 54th minute, from a Walker corner, Barcham's stooping header drew a routine stop from Flinders.
The first Scunthorpe change of the afternoon came a minute later as Jennings came on for Ryan, who had been on the ground receiving treatment moments before.
Walker had a chance seconds later as he saw his powerful effort from 30 yards tipped over by Flinders.
In the 59th minute, Barcham beat Neil Austin to the ball and took it around the Pools right-back before curling an effort which the Hartlepool custodian gathered.
On 65 minutes, Barcham was again in the thick of the action, as his cross forced Flinders to punch the ball out - but only as far as Duffy, whose volley was deflected over the crossbar.
Then, the home goalkeeper made light work of saving Mirfin's header from a subsequent Walker corner.
Just two minutes later, Grella failed to get on the end of a chipped Jennings cross into the six-yard box after he'd been played through by Duffy.
The hosts very nearly caught Slocombe off guard in the 68th minute when Franks' right-wing cross almost snuck above him at his near post but it hit the top of the netting.
The next substitution soon arrived as Keegan came on for Barcham.
The game entered another quiet spell before exploding into life ten minutes from time.
Walker was sent off as he handled a shot on the goal-line, stopping it from going in.
Then, Steve Howard stepped up to take the subsequent penalty, which Slocombe saved, diving down to his right.
The away team, though down to ten men, were boosted by the save and Duffy was next to come close, drilling an effort towards goal which Flinders saved well.
Nevertheless, the scoring was completed in the 85th minute as Monkhouse took control of the ball down the right and craftily played in Luke James, who volleyed past Slocombe.
Horwood had the final chance of the afternoon, with a free-kick from 20 yards, which Slocombe saved well.
There were three minutes of stoppage time but neither side fashioned out any more chances.
The Iron are next in action on Tuesday night when they host Notts County in the first round of the Johnstone's Paint Trophy.
Hartlepool United: Flinders, Austin, Collins, Hartley, Horwood, Franks (Holden, 70), Murray, Sweeney, Monkhouse, Howard, Poole (James, 63).
Substitutes not used: McHugh, Baldwin, Humphreys, Luscombe, Walton.
Scunthorpe United: Slocombe, Ribeiro, Mirfin, Canavan, Newey, Prutton, Walker, Ryan (Jennings, 55), Duffy, Barcham (Keegan, 70), Grella.
Substitutes not used: Severn, Gibbons, Hughes, Howe.
Attendance: 3,863 (234 away).