Chris Wilder's return to Halifax saw him taste defeat as Blades boss for the first time.
Second half goals from Connor Hughes and Richard Peniket saw the Blades beaten by the National League side.
The home team were the quicker out of the blocks and struck the woodwork inside seven minutes, Sinnott crashing a shot against a post.
After a slow opening the Blades came more into the game, Duffy shot at goalkeeper Drench and then Basham headed wide a right-wing cross.
The home goalkeeper made an impressive save from a stretching Coutts volley and the final kick off the half saw Done fire against the base of a post.
There was little in terms of chances early in the second half, apart from Drench clawing away a Done cross, before the substitutions began just before the hour mark.
Wilson came close to turning Hussey's corner in and Burrow clipped over the crossbar after a mistake by Wright.
The changes, on both sides, continued and on 76 minutes the home side grabbed the lead. A move from right to left, involving Moyo, saw HUGHES perfectly place a low show beyond the left arm of the diving Ramsdale.
Hughes then turned provider on 83 minutes as Halifax doubled their lead; the Blades failed to clear a corner and PENIKET netted at the back post.
Late on Scougall curled a free-kick over the crossbar and McNulty fired a set-piece into the wall, just before the final whistle.
Halifax: Drench, Moyo, Wilde, King, Hone, Garner, MacDonald, Hibbs, Denton, Burrow, Sinnott.
Subs: Nicholson, Peniket, Hughes, Kosylo, Hotte, Jackson, Baldwin, Harrison, Roberts, Khan.
Blades: Ramsdale, Brayford (Freeman 70), Hussey (K Wallace 70), Fleck (Reed 58), O'Connell (Wright 70), Basham (Whiteman 70), Sharp (McNulty 58), Done (Brooks 70), Coutts (Scougall 58), Wilson, Duffy (Calvert-Lewin 58).
Unused: Long, Walters.