The global policing agency, in a release, said only that its general secretariat received Meng's resignation on Sunday, effective immediately. It did not say why.
Meng is also a vice minister of public security in China.
According to the Associated Press, Grace Meng, Meng Hongwei's wife, reported on October 5 that she hadn't heard from her husband since September 25, when her husband was on a trip back to China.
On Sunday, a statement from China's ruling Communist Party said Meng was "under the monitoring and investigation" of China's new anti-corruption unit, the National Supervision Commission, for suspected serious violations of state law.
Senior Vice President Kim Jong Yang of South Korea will become acting president, pending the election of a successor.
Under President Xi Jinping, China has been engaged in a crackdown on corruption.
Amid reports of missing Interpol president Meng Wonghei being detained in China, the worldwide police organisation announced on Sunday that it has received the resignation of its Chinese chief Meng Hongwei.
The reports quoted an unnamed French judicial official as saying that Meng arrived in China at the end of September but there had been no news of him since.
Soon after the CCDI made public Meng's status, Grace Meng, who first learned about the development from the AP, said she was struggling to believe what it said.
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Critics of Meng's 2016 election to Interpol's presidency said he would use the position to help China target dissidents overseas under the guise of pursuing corrupt officials.
Speaking to reporters Sunday in France, Meng´s wife said she feared that her husband´s life was in danger. Using his Interpol mobile phone, he sent her the emoji image of a kitchen knife that day, four minutes after he sent a message saying, "Wait for my call".
"I'm not sure what has happened to him", she said.
It's not clear exactly what sort of crimes Meng is being accused of, but it's hard to see a good outcome for either him or China.
Earlier Interpol had indicated Meng's disappearance was "for the relevant authorities in France and China" to deal with.
After China admitted it had Meng in custody, the paper quoted Beijing-based political commentator Zhang Lifan, who said: "I guess something urgent must have happened".
The Interpol statement did not say exactly why Meng resigned.
"His job is very busy", she said.
A source familiar with the investigation said the working assumption was that the 64-year-old had antagonised Chinese authorities and had been detained as a result.