The debate over who is better out of Ronaldo or Barca counterpart Lionel Messi has raged for some time now, but unlike the former, the latter has always been able to call on an impeccable record in this fixture.
On Saturday night, though, Ronaldo stepped up, scoring a 73rd-minute winner that puts Jose Mourinho's men seven points clear of their old foes at the top of the table with four games remaining.
He struck just two minutes after Alexis Sanchez had bundled in an equaliser to cancel out Sami Khedira's equally scrappy first-half opener - a goal that set a new record for goals in a league season.
It was the Portugal forward's standout contribution on a night when Madrid, humiliated 5-1 on this ground last season, strangled their normally free-passing hosts.
Messi was barely allowed a kick and his playmaking team-mates - Xavi and Andres Iniesta - were largely stifled by a Madrid side fully aware of the rewards on offer.
Mourinho shaved his head at the start of the week to signal he was ready to "go to war", but the game never really ignited to such levels.
There were chances - Barca rookie Cristian Tello wasting a number of them - but the gameplan laid out by the Portuguese coach was clearly to drain the life out of the home side.
It worked a treat and, at times, allowed his men to look like the passing team.
They started well, with Ronaldo's fourth-minute header forcing Victor Valdes into a full-stretch save and Karim Benzema cutting in from the right and drilling in an effort that the keeper dealt with.
Madrid were enjoying making full use of the Nou Camp's wide pitch and, when Ronaldo burned past Sergio Busquets on the left, the midfielder hauled him down and picked up the game's first booking.
That was indicative of the early promise Real had shown and, with 17 minutes on the clock, they took the lead with their 108th goal of the campaign.
Mesut Ozil's corner found Pepe at the back post and his header was parried by Valdes but, as Carles Puyol struggled to get his legs free to clear, Khedira wrapped his foot around the loose ball to score from two yards.
Replays suggested the ball may have clipped Pepe's arm as he nodded down, but any decision to rule out the strike would have been harsh.
The goal was met with near silence, much like when Xavi missed a wonderful chance to equalise 10 minutes later.
Messi's slide-rule pass put him clear on Iker Casillas' goal, but he could only hit across and wide, rather than under the keeper as was expected.
Swamped whenever they had the ball, Barca resorted to shooting from distance through Thiago, while at the other end Ozil's pace got him clear, with Javier Mascherano's brilliant block halting his run.
Whether directed at half-time by Mourinho or not, Real returned for the second half with the intention of slowing the game down, with a number of players including Pepe and Fabio Coentrao both requiring treatment for what appeared to be innocuous injuries.
Their tactics were frustrating Barcelona, though, who could barely get close to Casillas' goal and, when they did, Tello twice hit wildly over - the second occasion a horrendous spoon that cleared the bar.
But Tello was persistent, and in the 70th minute, he helped Barcelona get level.
The goal had an element of pinball about it, with Casillas denying Tello and Sanchez in quick succession - the second save a wonderful claw-back - before the Chilean eventually bundled in from close range.
But, rather than implode as they have done so often in this fixture over recent years, Real responded with class.
Ozil's ball set Ronaldo racing down the right and past Mascherano, although his 54th goal of the season was made easier by Valdes' decision to race off his line.
Clearly stunned, Barca offered no response of note and it was Real who finished the stronger, with Ronaldo inches away from adding a crowning third in stoppage time.