Los Blancos' French centre-back produced an exemplary performance, which included a fine late goal, to help cancel out the Blaugrana's opener early in the second half
The Catalan side looked to have put one foot in the final as they led late on after Cesc Fabregas had put them 1-0 up with a well-taken goal shortly after the break, only for Madrid's young defender Varane to secure the home team a draw in the 81st minute.
Madrid were without five first-team players for their fourth Clasico of the season, as Iker Casillas and Pepe missed out because of injury, while the likes of Sergio Ramos, Fabio Coentrao and Angel Di Maria were all absent through suspension. Barcelona, meanwhile, named a full-strength starting line-up, with Jose Pinto retaining his place in goal, as he has done for the Copa del Rey.
For all their missing men it was los Blancos that made the brighter start of the two sides. Within a minute of kick-off Ronaldo was charging at the heart of the Barcelona defence, and his driving run towards goal was only stopped by a cynical challenge from Gerard Pique. The Portuguese attacker took the set piece himself and proceeded to force Pinto into making a fine diving stop.
In the 12th minute a moment of mastery from Andres Iniesta created a chance for the overlapping Jordi Alba, but the Barcelona left-back could only volley wide of Diego Lopez's goal after bursting through the Madrid defence and connecting with Iniesta's effortless chipped pass.
Moments after being booked for a mistimed challenge on Cesc Fabregas, Ricardo Carvalho bundled into Iniesta 25 yards from goal, and from the resulting free kick Xavi came within inches of giving Barcelona the lead, as his devilish curling effort rattled the crossbar with Lopez beaten.
Carvalho then nearly supplied an assist for Barcelona when his tame back-pass allowed Messi to steal the ball and tee up Xavi inside the Madrid box. The Barcelona midfielder arrowed a shot towards the bottom left corner but Madrid's young centre-back Varane was there on the line to brilliantly hack Xavi's goal-bound strike away from danger.
On the half hour mark, Karim Benzema nearly scored for the home side when he found space in behind the Barcelona back-line to meet Jose Callejon's superb pass and send a volley crashing into the side-netting from a tight angle.
Somehow, a frantic opening first half ended 0-0 despite an avalanche of chances being created by two teams putting clear emphasis on attack rather than defence.
Madrid mimicked their strong start to the first half after the break and fashioned a chance after just 40 seconds of the second period - Benzema hammering a shot over 18 yards from goal.
Despite their pressure Madrid found themselves a goal behind in the 50th minute when Fabregas clinically side-footed the ball past Lopez after being played in by Messi. Just a single touch was needed by Messi to both dispossess Xabi Alonso and play a weighted through ball into the path of Fabregas, with the former Arsenal captain producing a cool finish to give the Catalan side a 1-0 lead.
Then, if not for a sumptuously timed challenge from Varane, Fabregas could well have given Barcelona a two-goal lead. The Frenchman's tackle on his opponent brought Jose Mourinho to his feet, and prompted the coach to make an immediate change with his team on the back foot - introducing Luka Modric for Callejon.
Ronaldo then missed a glorious opportunity to head Madrid level from close range, but he could not test Pinto after connecting with Essien's teasing cross from the right.
Pique, perhaps not to be outshone by Varane up the other end, then produced an equally brilliant tackle on Ronaldo as the Portugal international shaped to send a shot goalwards inside the Barcelona penalty area.
With Barcelona seemingly set to hold out for the win, up popped Varane in the 81st minute to rise highest and send an emphatic header past Pinto from Mesut Ozil's free kick to make it 1-1 and set up an enticing second leg at Camp Nou on February 26.