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"We should have scored in the first half... Now we must beat France," said Mexico's coach Javier Aguirre.
Carlos Vela comfortably converted a corner for the visitors in the 37th minute, which was cancelled out for offside.
Giovani Dos Santos, 21, became the soul of the Mexican squad. He was not far from giving hosts the worst possible start but his strike, after Khune spilled a cross into his way, was deflected by South African captain Aaron Mokoena after only two minutes.
Mexicans kept on piling up pressure as Vela, Dos Santos and Guillermo Franco tested Khune in roll. But Bafana Bafana showed a glimpse of talent as Katlego Mphela just missed connecting with Siphiwe Tshabalala's left-wing cross one minute from the break.
The second half wrote a different story when a superb through-ball sent Tshablala pacing down the left before he walloped a sizzling left-foot shot into the far top corner. He performed a dance to celebrate with his team-mates, accompanied by great outpouring of emotions from the packed stands.
The South Africans were ready to celebrate a win, but Marquez ultimately denied their carnival. He controlled Andres Guardado's cross at the back post and rifled past Khune to ensure the spoils were shared after a breathless opening to the tournament.
However, hosts have left their mark in the world cup history as they've made a first important step to hold a successful event with a smooth start and a fantastic opening ceremony, which featured fighter jets' aerial introduction and colorful Africa-flavored performance.