There was nothing to separate the Ballon d'Or hopefuls as after giving the visitors the lead, the Portuguese earned his side a point following a brace from the Argentine superstar
Despite coming as just the seventh fixture of the season, the match was touted as having a potentially huge impact on the final Liga outcome. With Madrid in need of a win, Ronaldo got them off to the perfect start as he silenced the crowd with his sixth consecutive Clasico goal.
But a brace from Messi, including a sumptuous second-half free kick, put the Blaugrana in the driving seat. However, the last had not been heard of Ronaldo and he capitalised on a disorganised defence to equalise 25 minutes from time.
After all the intense build-up, the first surprise of the night was sprung as news filtered through that in the absence of Gerard Pique and Carles Puyol, Adriano would start alongside Javier Mascherano in the centre of defence. Mourinho, meanwhile, opted for Karim Benzema and Mesut Ozil ahead of Gonzalo Higuain and Mesut Ozil.
The teams were greeted on the pitch by a cacophony of noise and a sea of Catalan red and yellow in the stands and the match began in a similarly hectic manner, but Los Blancos' more adventurous tendencies when in possession saw them gradually take hold of the game.
After Benzema snatched at a volley in the 13th minute, Barca's defensive frailties began to really show six minutes later as Sergio Ramos rose, unmarked, to meet Ozil's corner. His header had pace and Victor Valdes, who was rooted to the spot, breathed a sigh of relief when it shaded the outside of his post.
Despite enjoying a large share of possession, the hosts began to sit deep and invite Mourinho's men onto them, and they were punished in the 23rd minute. A brilliant flowing move, initiated by Ozil on the right, ended with Benzema slipping the ball to Ronaldo who thumped a low shot past Valdes at his near post.
Madrid continued to slice apart the hosts' makeshift defence with ease and they should have doubled their lead in the 25th minute. Benzema once more found space in the area but his shot cannoned back off the post and Angel Di Maria was unable to convert the rebound.
Yet the Blaugrana were unperturbed at the other end of the pitch and they secured an equaliser when Pedro's cross looped into the air following a pair of deflections. In his eagerness to head the ball away, Pepe misjudged the flight of the ball and Messi, who was lurking in the box, beat Iker Casillas as it dropped behind the defender and fired into the back of the net.
The Catalan giants drew confidence from that goal and after being denied a penalty early in the second half, they took the lead for the first time on the night with a moment of sheer, unadulterated class from Messi. The mercurial Argentine flighted a beautifully-struck 30-yard free kick over the wall and into the top corner with 61 minutes on the clock.
Not to be outdone though, Ronaldo notched his second of the night just five minutes later. After being jeered by the home crowd for missing an overhead kick, the 27-year-old caught the Barca defence completely unawares to slot home from Ozil's through-ball.
With the game so finely poised, neither team was willing to take the risk of committing too many men forward in search of a winner. But there was still time for some final moments of drama as Martin Montoya pushed on but saw his rocket of a strike come back off the crossbar in the 89th minute and Pedro drilled a low shot wide in stoppage time.
In sharing the spoils, Barcelona remain at the top of the table and also maintain their eight-point advantage over Madrid with seven games played so far this season.