Meng Hongwei, according to Chinese state news agency Xinhua, was the first Chinese official to become president of Interpol, which is based in Lyon.
"Today, Sunday 7 October, (at) the Interpol General Secretariat in Lyon, France received the resignation of Mr Meng Hongwei as President of Interpol with immediate effect", Interpol said in a statement.
She said she hadn't heard from her husband since September 25.
His family lost touch with him after he travelled from France, where Interpol is based, to China.
The last person in contact with the 64-year-old Meng was his wife, who told reporters prior to China's announcement that she had received a WhatsApp message from him containing nothing but a knife emoji after he had arrived in China, which came several minutes after a message which said,"wait for my call".
"I'm pretty sure they would have expected an extraordinary response from the global community before taking such a decision", he told the Post.
Asked if she believed that he has been arrested, Grace Meng said: "In China, what happened, I'm not sure".
Meng's wife said he had traveled back to China for work, after a visit to the Nordics.
Earlier on Sunday, China officially confirmed that the Chinese head of the Interpol is being investigated for suspected breach of law. In the end, China clearly decided that his role at Interpol did not prevent them from detaining him and not even admitting it for days.
This photo shows the last message sent by missing Interpol President, Meng Hongwei, to his wife, Grace Meng.
Ms Meng read a statement during her press conference, but would not allow reporters to show her face, saying she feared for her own safety and the safety of her two children.
Of the knife image, she said: "I think he means he is in danger".
Mrs. Meng declined to speculate on her husband's whereabouts.
She said he had sent her a message with a knife emoticon on her mobile phone signifying he was in danger.
The French ministry, however, said that they did not have any information regarding that.
The campaign has since punished over 1 million officials of varying stature, who are often suddenly detained without warning only to emerge later in detention.
Xi, China's most powerful leader since Mao Zedong, has overseen a harsh crackdown on civil society that is aimed at squelching dissent and activism among lawyers and rights advocates. He is a senior member of the Communist Party.