Luz is quoted by the French newspaper Liberation as saying that his job had become “too much to bear” following the deaths of his colleagues.
Twelve people were murdered when two Islamist gunmen burst into the Charlie Hebdo offices on January 7.
“Each issue is torture because the others are gone,” Luz told Liberation.
Luz joined Charlie Hebdo in 1992 and said his resignation was “a very personal choice”. He will leave in September.
“Spending sleepless nights summoning the dead, wondering what Charb, Cabu, Honore, Tignous would have done is exhausting,” he added.
Within days of the attack, Charlie Hebdo‘s surviving staff produced an edition with the headline “All is forgiven” above Luz’s cartoon of Prophet Muhammad holding a sign saying “Je suis Charlie”.
Pictorial depictions of Prophet Muhammad are considered forbidden by most Muslims.
Last month, Luz announced he would stop drawing images of Muhammad, as it no longer interested him.
He announced his plans to leave on May 18, but said many people were urging him to stay.
“They forget that the worry is finding inspiration,” he added.
Charlie Hebdo, which regularly struggled to make ends meet, is now backed up by tens of millions of euros of funding.
Luz said in a previous interview that financial security had posed questions about its future editorial direction.
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