The Spain international had been sidelined since October with a knee complaint.
Having been welcomed back to training in the week building up to a crunch meeting with Los Blancos, the World Cup winner was eased back into the fold with a starting position on the bench.
Luis Enrique waited until just before the hour mark before turning to the midfielder, with Ivan Rakitic making way.
Iniesta was given a rousing welcome by the Catalan natives upon his introduction, with the 32-year-old inheriting the captain’s armband.
Lionel Messi had skippered Barca for the first time in a Clasico fixture in the absence of his club captain, but was more than happy to pass the baton back to his illustrious colleague.