Interpol had said it had asked Beijing to clarify Meng's situation.
The Interpol General Secretariat in Lyon, France received the resignation of the organization's president, Meng Hongwei, 64, effective immediately, Interpol said in a statement Sunday. It did not say why.
While Meng's "disappearance" first made worldwide news on Friday.
However, China's anti-graft watchdog said late on Sunday that the Chinese authorities were investigating for suspected violations of the law.
Interpol said South Korean national Kim Jong Yang would becomes its acting president, while it would appoint a new president at a 18-21 November meeting of the organisation in Dubai.
The disciplinary organ of China's ruling Communist Party says the head of Interpol, a senior Chinese official, is under investigation on suspicion of unspecified legal violations.
Previously, Interpol had said that reports about Meng's disappearance were "a matter for the relevant authorities in both France and China". The message from Meng at 12:26 on September 26 says "wait for my call".
Mr Meng's duties in China would have put him in close proximity to many former leaders, some of whom had come into difficulty with President Xi Jinping's crackdown on corruption.
Grace Meng told reporters in Lyon, France, that she thinks her husband was trying to tell her he was in danger.
Speaking today, Mrs Meng said she has had no further contact with her husband since the message with a knife image inside was sent on September 25.
Four minutes before he sent the knife emoticon image, he sent his wife a text message saying: "Wait for my call".
The mystery of what happened to Mr Meng has now been cleared up: but the details of the charges weighing against him, and the fate that awaits him are as opaque as ever, says the BBC's Hugh Schofield in Paris.
Meng had lived with his wife and two children in Lyon since being elected Interpol president in 2016.
Presidents of Interpol are seconded from their national administrations and remain in their home post while representing the worldwide policing body.
In the role Meng has been entrusted with a number of sensitive portfolios, including heading up the country's counter-terrorism division, which saw him in charge of the response to several major incidents in China's fractious western region of Xinjiang.
"I have gone from sorrow and fear to the pursuit of truth, justice, and responsibility toward history", she said.
French police announced on Friday that they were leading investigations to find Mr Meng.
She kept her back turned to the reporters at the press conference, and refused to be photographed out of fear for her safety. The matter belongs to the global community.