The game was Barcelona's last real test in remaining unbeaten during a whole La Liga campaign.
Ernesto Valverde's side now need to avoid a loss in their final three fixtures - two of which are at home - and the most hard of those was the visit of Real.
With Barcelona already Spanish league champion and Madrid focused on its Champions League final later this month, it was supposed to be the most low-key "clasico" in years.
Messi earned himself a booking when he went in late on Ramos shortly afterwards and Sergi Roberto was sent off in injury time for hitting Marcelo with an arm to the face.
Lionel Messi put 10-man Barca back in front, although Gareth Bale's 13th league goal of the season restored parity 18 minutes from time.
An incredible ovation followed, as the player who helped define a generation for club and country said farewell to LaLiga's biggest match, his substitution around the hour mark a common sight this season.
Barca exploded out of the blocks and they were ahead within 10 minutes.
Rivals Barcelona and Real Madrid showed Sunday that they don't need titles at stake to produce a thrilling game of football.
Barca were reduced to 10 men after Sergi Roberto was shown a straight red card after he appeared to slap Real defender Marcelo.
Bale was practically invisible during the first half of Sunday's Clasico, while team-mate Ronaldo had several chances to add to his one goal but was clearly held back by his knock.
Messi was stopped by goalkeeper Keylor Navas from scoring again and Gareth Bale pulled Madrid level in the 72nd after curling in a pass by substitute Marco Asensio. As such a key part of Barca's successes during his years at the Nou Camp, he will be a tough act to follow.
The final stages of the second half were lively, although neither side could find a winning goal and the spoils were shared on the evening, with Barca keeping their hunt for an unbeaten LaLiga season intact.
Zinedine Zidane's nightmare, far more than a defeat at Camp Nou, would surely have been to lose Cristiano Ronaldo to injury less than three weeks before the Champions League final.
This meeting of La Liga's two most glamorous clubs will have minimal affect on the table, given Barca are unassailable and Real, now concentrating on the Champions League final, are safe inside the top four. There was the important save from Marc-Andre ter Stegen, who denied Ronaldo early on.
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