Battling Scunthorpe grabbed an unlikely lead through a Myles Hippolyte penalty on 15 minutes.
But Clarke goals on 28 and 60 minutes, sandwiching a finish by Jordan Bowery in first half injury time saw Nigel Clough's men deservedly home to three more points.
Rhys Oates and George Lapslie missed out with the injuries they picked up at Stevenage last weekend, replaced by Jordan Bowery and Ryan Stirk.
But George Maris was passed fit after his knee injury from last week and Kellan Gordon's return from injury to the bench was also a welcome sight for the home side.
Stags started well and on five minutes Charlsley had a finish blocked by Onariase after good work by Maris and a low cross from Bowery.
There was a hold-up after Clarke took a knock to the head, but he was able to continue.
O'Hara had his first save to make on 10 minutes when he turned over a dipping Hewitt header from a McLaughlin free kick.
And as United tried to clear the corer, Quinn fed Maris, who shot wide of the near post.
But all the early good work was undone when United went ahead from the spot on 15 minutes from their first serious raid.
Stags were undone by a quality pass down the centre by Hackney that put Hippolyte in on goal. He was brought down by keeper Bishop as he tried to go round him and picked himself up to send Bishop the wrong way from the penalty.
Quinn then put in a great cross which Chatrsley headed back in front of goal, but no Stags players were there to capitalise as the ball was hacked clear.
But Loft's persistence almost doubled United's lead on 19 minutes as he held off O'Toole in a battle down the middle and pulled a low finish just wide.
A minute later Charsley sent Bowery clear into the box, but although his low finish beat O'Hara's dive, it came back off the post.
McLaughlin then saw a low blast deflect just wide.
Stags were deservedly level on 28 minutes from a move started and finished by skipper Clarke. He finally made space on the edge of the box and drilled the ball low inside the right post.
Mansfield kept pressing and on 39 minutes Maris' pass picked out Bowery in the box, but his finish was always rising well over.
Three minutes later the Iron won their first corner of the contest and, taken by O'Malley, it was headed over by Onariase.
Home players and fans were then angry that play was waved on when it had appeared a Scunthorpe player had handled and Scrimshaw ran on to shoot in the sidenetting.
Two minutes were added on and in the first of those Stags went ahead for the first time.
McLaughlin pulled back a cross from the left which saw Charsley fire goalwards.
O'Hara made a good save and when Bowery met the lose ball, O'Hara again got his hands to it but the ball spun on into the gaping net.
There was still time for Maris to shoot low and wide from another neat home move.
Scunthorpe almost levelled seven minutes into the second half as Loft burst impressively down the left only to see Bishop alert to block as he tried to beat him low at his neat post.
A minute later Stirk fed Clarke in the United box, but the skipper missed his kick with only the keeper to beat.
But Clarke was the hero on the hour as he robbed a dithering Perry 25 yards from goal and ran on to slot home a low finish.
Young striker Gale was given a league debut on 69 minutes as Bowery limped off.
Hippolyte was well over after cutting in from the right on 77 minutes as Scunthorpe desperately looked for a lifeline.
A minute later they came even closer as O'Malley's 25 yard free kick looked destined for the top right corner only for Bishop to reach it, catch and hold on.
Sinclair then warmed O'Hara's hands with a low shot from a tight angle.
Finding his feet, a good run by Gale to the right by-line saw him cross low but Charsley unable to turn home from close range.
Pugh, halting a Stags break with a foul two minutes into added time, saw the game's first and only yellow card as Stags coasted to a deserved victory.
STAGS: Bishop, Hewitt, O'Toole, Hawkins, McLaughlin, Charsley, O.Clarke, Maris, Quinn (Sinclair 61), Stirk (Forrester 88), Bowery (Gale 69). SUBS NOT USED: Shelvey, Rawson, Gordon, Law
SCUNTHORPE: O'Hara, O'Malley, Kenyon (Beestin 61), Taft, Onariase, Loft (Jarvis 73), Hippolyte, Rowe, Scrimshaw, Perry (Jarvis 78), Hackney. SUBS NOT USED: Collins, Millen, Green, Thompson.
REFEREE: Benjamin Speedie.
ATTENDANCE:4,904 (528 away).