Sharp began his career at Sheffield United in 2004 and is now enjoying his third spell with the club, having played up and down the football league, most notably for Doncaster and Scunthorpe.
Pierre-Michel Lasogga restored parity for Leeds in the second half with a header, before Sharp stepped up to score the victor from the penalty spot after John Fleck had been fouled by skipper Eunan O'Kane.
Historically, the North London derby isn't an easy game to predict.
And as in the earlier game it was former Leeds striker Billy Sharp who did the damage, this time with a spectacular overhead volley from 15 yards out after a Mark Duffy cross had not been cleared by O'Kane.
The hosts got off to a flying start when Sharp scored against his former club in only the second minute.
This match started in nightmare fashion as an unmarked Billy Sharp volleyed in an impressive goal after Duffy's unchallenged cross was deflected by Eunan O'Kane into the box.
Leeds struggled to muster any response and two speculative efforts from Gjanni Alioski, both from a hopeful range, failed to trouble Sheffield United goalkeeper Jamal Blackman.
Leeds were stung in the first two minutes when Sharp found the back of the net, but they managed to respond just after the half-time break through Pierre-Michel Lasogga.
The home side started to get a bit more pressure after Pablo Hernandez had released Kalvin Phillips in the Sheffield United box, only for Blackman to come out and grab the good attempt.
A handball in the box was ignored later on in the second half, but Leeds showed nearly no life in the first half until Pablo Hernandez was introduced near halftime after Kemar Roofe left after sustaining an injury.
Pierre-Michel Lasogga levelled the tie just after the restart when he headed home, although it proved to not be enough to get at least a point from the game.
Sharp also played for Leeds during the 2014/15 season but showed no interest in a muted celebration after scoring this stunner. It was another moment of lackadaisical application and a definite "eyes-shut" moment as a well-worked free-kick into the Leeds area saw Eunan O'Kane's hapless challenge result in a penalty.
Sheffield United: Blackman, Baldock, Basham, O'Connell, Stearman, Stevens, Evans (Lundstram), Fleck, Duffy (Leonard 77), Sharp (Holmes 89), Clarke.
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