David Brooks' first goal for Sheffield United clinched a 2-1 win at Yorkshire rivals and sent them top of the Sky Bet Championship.
Second-half substitute Brooks fired home a low angled shot late in the game after Kalvin Phillips had cancelled out Blades striker Billy Sharps' opener against his former club.
Victory for Chris Wilder's side, automatically promoted from League One in May, is their eighth in their last 10 league games and lifted them top of the second tier for the first time since November 2005.
Leeds demonstrated their new community relations under owner Andrea Radrizzani before kick-off as both teams were led out by four-year-old local fan Toby Nye and his brother Ollie.
Toby is fighting cancer and, after being denied treatment by the NHS, Leeds have pledged to help raise the £200,000 required. Players and club office staff have donated Friday's wages to the youngster's cause.
The Blades however, left their goodwill off the pitch. They tore into Leeds from the very first whistle and stormed into a second-minute lead.
Mark Duffy's cross from the right caught Leeds cold and Sharp, unmarked at the far post, headed his sixth league goal of the season.
Blades striker Leon Clarke just failed to connect with another ball in from Duffy and a series of crosses forced Leeds into some frantic defending.
Only Andy Lonergan's brilliant reaction save denied Sharp a second from Clarke's pin-point cross after Matthew Pennington's blunder as Leeds were in danger of being swept away.
But Thomas Christiansen's side stemmed the tide with a superbly-taken equaliser in the 35th minute.
Ezgjan Alioski's cross was only half headed clear by Blades defender Cameron Carter-Vickers and Phillips slammed home a sweetly-struck volley from the edge of the area.
Sharp was left cursing again shortly before half-time when he sprang the offside trap from Duffy's quickly-taken free-kick, only for Lonergan to rescue Leeds with another fine save.
Pontuss Jansson replaced injured Leeds skipper Liam Cooper in the 56th minute before Samuel Saiz almost put the hosts ahead with a thumping 20-yard effort, which struck Jamal Blackman's left-hand post.
The home side were enjoying their best spell, but Phillips wasted a decent chance when slipping as he took a free-kick and was then booked by referee Scott Duncan for his crude challenge on George Baldock.
Alioski squandered another Leeds chance when he headed straight at Blackman following Saiz's cross to the far post and was replaced by Pablo Hernandez soon after.
Saiz had been instrumental in Leeds gaining a second-half edge and while clear-cut chances at both ends had dried up, a pulsating derby hung in the balance as the game entered the final 15 minutes.
Sharp made way for Brooks in the 75th minute and six minutes later, after Clarke had volleyed Enda Stevens' cross straight at Lonergan, the Blades substitute fired his side ahead for the second time.
Duffy set Brooks clear on the left edge of the penalty area and the latter steered home a low shot into the far corner.
Leeds pressed forward in search of another equaliser, but the Blades held out to reach the Championship summit for the first time in 12 years.