Misbah ended a Test century drought dating back to May 2011 as he struck 100 off 187 balls to help the de facto hosts to 429 for eight at tea - a lead of 180 runs - at the Sheikh Zayed Stadium.
Misbah had no sooner reached his century before he was trapped lbw by Dale Steyn to become one of four wickets to tumble in the afternoon session.
Prior to his demise, Misbah had added 112 runs with Khurram Manzoor (146), who was the only victim of the morning session after holing out to Jaques Kallis off Vernon Philander.
Misbah then joined with Asad Shafiq to add a further 82 runs before the latter was removed on 54 after chipping to Alviro Petersen at short midwicket.
Saeed Ajmal (13) and Zulfiqar Babar (two) also fell before tea as South Africa finally began to get some joy on a docile surface.
Adnan Akmal remained unbeaten on 22 at tea.