Three million copies are being printed – a week after Islamist gunmen murdered 8 journalists at the magazine and four other people in Paris.
The cartoon shows the Prophet weeping while holding a sign saying “Je suis Charlie” (“I am Charlie”).
It is believed earlier cartoons of Prophet Muhammad prompted the attack.
The slogan “Je suis Charlie” has been widely used following the shootings.
In a separate attack in Paris two days later, four Jewish men died after an Islamist gunmen took hostages at a kosher shop in the French capital. A police woman was shot dead in a third shooting believed to have been carried out by the same attacker.
Wednesday’s edition of Charlie Hebdo has an unprecedented print run of three million copies. Normally only 60,000 are printed each week.
Demand for what is being called the “survivor’s issue” of the magazine is high, correspondents say, especially as the proceeds will go to the victims’ families.
People could be seen queuing outside newsstands on Wednesday morning to buy copies.
Kiosk owners told French media they had received large numbers of reservation requests, while at one shop in Paris all copies were reportedly sold out within 30 minutes.
The issue is available in six languages – including English, Arabic and Turkish – some in print and some online.
Editor-in-chief Gerard Biard told reporters: “We are happy to have done it and happy to have been able to do it, to have achieved it. It was tough. The front page… was complicated to put together, because it had to express something new, it had to say something relating to the event that we had to deal with.”
The front cover of the edition had been widely published in advance by French media.
Outside France, the Washington Post, Germany’s Frankfurter Allgemeine, Corriere della Sera in Italy and the UK’s Guardian are among publications to show the cartoon.
Very few outlets in the Middle East and North Africa have shown the image.
Charlie Hebdo‘s decision to publish another cartoon of the Prophet has already generated threats from militant Islamist websites and criticism from the Islamic world.
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