A youthful Handsworth side condemned AFC to their fourth straight league defeat despite a late resurgence from the Bulls.
Jack Warner and Ross Duggan got on the scoresheet on either side of half-time, but not at the right moments as Handsworth were in front from very early on.
Johnny Pugh marked the game's first attempt on goal after successfully chasing the ball down the left before cutting inside, but his curling effort was deflected over the crossbar.
Only two minutes later, the visitors were ahead.
Josh Dacre converted from close range after Marley Grant headed down Handsworth's second corner of the game.
Down the other end, it could have quickly been all square, but Ross Duggan was flagged offside after Jordan Annable delivered an inch-perfect ball to his feet deep inside the Ambers penalty area.
Looking dangerous on the break, the visitors were quick to add to their advantage when Ehsan Mohamed turned and curled into the far corner after the Ambers countered to Ross Duggan's unsuccessful free-kick.
Meanwhile the Bulls struggled for clear chances, and Brett Lucas's free-kick curling just over the bar from 25 yards was the closest they came to halving the deficit within the first half an hour.
But the chances eventually came, and Jack Warner brought the Bulls back into the game when he latched onto a perfectly pinged long ball and forced the ball past Ben Townsend at his near post.
A short dominant spell then followed for AFC, but they were once again punished for errors at the back as Johnny Pugh robbed Brett Lucas and fired home with just Warhurst to beat.
The game continued to be an uphill battle for Matt Chatfield's side in the second half, with Handsworth pushing for a fourth and almost finding it when Warhurst had to wrestle hard to win the ball from the feet of substitute Joe Parkin in his goal mouth.
With less than 20 minutes remaining on the clock Grant Ryan had a rare opportunity to once again drag the hosts back into the contest, but he couldn't direct skipper Buxton's cross on target.
Having struggled for goals over the last few games, it was a breath of fresh air to score a second in the same fixture, and substitute Brandon Webster did all the legwork with a textbook dribble past his man before firing in a killer ball for Ross Duggan to tap home.
Duggan then almost completed the comeback, but instead forced a fine save from Ben Townsend from inside the penalty area.
The Bulls pushed hard for a leveller but were cruelly dismissed in the sixth minute of injury time, as Leon Howarth chased a loose ball with all but Hugo Warhurst committed in the Ambers penalty area, rounded the AFC stopper and with the last kick of the game secured all three points for a deserving young Handsworth side.
Attention switches to the FA Vase on Saturday, when the Bulls host Long Buckby at Clipstone's Lido Ground.
Final score | AFC Mansfield 2-4 Handsworth
Scorers | Warner (30'), Duggan (75') - Dacre (4'), Mohamed (14'), Pugh (39'), Howarth (90'+6)
Bulls XI | Warhurst (GK), Annable, Slone, Buxton (C), Hough, Lucas (McMillan 78'), Warner, Corder, Duggan, Ryan, Dawson (Webster 69')
Unused subs | Williams, Hague, Parkin (GK)
Yellow cards | Buxton (60')
Handsworth XI | Townsend (GK), Smith, Eagle, Hobson, Varley, Dacre (Parkin 56'), Mohamed (Mitchell 87'), Mackie, Osborne (Howarth 65'), Grant, Pugh
Unused subs | Etia, Austin
Yellow cards | Eagle (45')
Man of the Match | Jack Warner
Attendance | TBC