The posters show a large picture of the Hungarian-born Jewish emigre laughing, alongside the text: "Let's not let Soros have the last laugh".
"I am distressed by the current Hungarian regime's use of anti-Semitic imagery as part of its deliberate disinformation campaign," the 86-year-old said in a rare statement.
The posters show a large picture of the Hungarian-born Jewish emigre laughing, alongside the text: "Let's not let Soros have the last laugh", a reference to government claims that Soros wants to force Hungary to allow in migrants.
Since the posters appeared on billboards and at public spaces around the country last week, as well as on television, several incidents of anti-Semitic graffiti such as "Stinking Jew" or Stars of David daubed on them have been reported.
Hungary's largest Jewish organisation, Mazsihisz, has called on Orban to stop the campaign, with its head Andras Heisler writing to Prime Minister Viktor Orban that the "poisonous messages harm the whole of Hungary".
Some opposition activists and citizens have also begun taking down some of the posters from billboards.
Soros said he was "heartened that together with countless fellow citizens the leadership of the Hungarian Jewish community" have spoken out.
Earlier Tuesday his spokesperson Michael Vachon called the campaign "reminiscent of Europe's darkest hours" with "clearly anti-Semitic overtones".
Those defacing the posters with graffiti "(understood) the government's intent," he said.
"The government has consistently and wilfully misrepresented Soros's views on migration and refugees," he added.
On Friday Orban accused Soros of being a "billionaire speculator" who wanted to use his wealth and civil groups that he supports to "settle a million migrants" in the European Union.
Orban and government officials say that Hungary has a policy of "zero tolerance" of anti-Semitism, and that the poster campaign is about increasing awareness of the "national security risk" posed by Soros.
On Saturday, Israel's ambassador in Budapest Yossi Amrani also criticised the poster campaign, saying it "evokes sad memories but also sows hatred and fear".
But late Sunday -- reportedly at the request of Prime Minister Benjamin Netanyahu's office -- Israel's foreign ministry issued a separate "clarification" that criticism of Soros was legitimate.
This said that while Israel "deplores" anti-Semitism, Soros "continuously undermines Israel's democratically elected governments by funding organisations that defame the Jewish state and seek to deny it the right to defend itself."
Netanyahu is due to visit Hungary next week, the first visit by an Israeli prime minister since the end of communism in 1989.