Meng has resigned “with immediate effect” and Senior Vice President Kim Jong Yang of South Korea has become acting president, Interpol said in a statement.
The announced resignation came hours after China said that Meng was under investigation for possible criminal activity as his wife voiced concern for his life after he sent her a final text message with a knife emoji.
Beijing had remained tight-lipped about the fate of Meng Hongwei, who is also China's vice minister for public security, since his disappearance was disclosed by French officials on Friday.
The National Supervisory Commission, which handles corruption cases involving public servants, broke the official silence early Monday, saying in a one-line statement that Meng “is currently under investigation on suspicion of violating the law”.
It is the latest high-profile disappearance in China, where a number of top government officials, billionaire business magnates and even an A-list celebrity have vanished for weeks or months at a time. When — or if — they reappear, it is often in court.
Meng, the first Chinese president of Interpol, was last heard from on September 25 as he left Lyon — where the international police organisation is based — for China.
The agency's secretary general Juergen Stock, who oversees day-to-day operations, had said Saturday that it was seeking “clarification” on his whereabouts from Chinese authorities.
French police had opened an investigation into Meng's disappearance last week, according to a source close to the inquiry.
Meng, 64, had lived with his wife and two children in France since being elected Interpol president in 2016.
Speaking to reporters in France on Sunday, Meng's wife Grace said she had received a message from his phone containing a knife emoji before his disappearance.
“This matter belongs to the international community,” she told a press conference.
That day, his wife said he sent a message telling her to “wait for my call”, before sending the emoji signifying danger.
“I'm not sure what has happened to him,” she told reporters before the anti-graft commission issued its statement.
Later, upon learning about the announcement from Chinese authorities, she told AFP that her husband's case will be under the watch of “international law and international public opinion”, describing the situation as “political ruin”.
China's recently established National Supervisory Commission holds sweeping powers to investigate the country's public servants with few requirements for transparency.
Although the commission did not detail the allegations against Meng, its mandate is to investigate corruption cases as part of Chinese President Xi Jinping's anti-graft campaign.
Some critics of the effort — which has punished more than one million officials — say it also functions as a tool for Xi to eliminate his political rivals.
Meng rose up the ranks of the country's domestic security apparatus when it was under the leadership of Zhou Yongkang, a rival to Xi and the highest-ranking official to be brought down on corruption charges.
Zhou — who was sentenced to life in prison in 2014 — was subsequently accused of conspiring to seize state power and authorities have continued working to root out his influence. He appointed Meng vice security minister in 2004.
In that role, Meng has been entrusted with a number of sensitive portfolios, including the country's counter-terrorism division, and he was in charge of the response to several major incidents in China's fractious western region of Xinjiang.
Critics of Meng's 2016 election to Interpol's presidency said he would use the position to help China target dissidents abroad under the guise of pursuing corrupt officials.
Interpol has downplayed the concerns, saying the president has little influence over the organisation's day-to-day operations, which are handled by secretary general Stock, a German.
The Chinese effort to track down corrupt officials abroad, known as Operation Fox Hunt, has led to claims in some countries that Chinese law-enforcement agents have been operating covertly on their soil without the approval or consent of local authorities.
China currently has 44 outstanding red notices, mostly related to murder, intentional injury and drug smuggling, according to Interpol's website.
During Meng's tenure, Interpol issued a red notice for fugitive Chinese billionaire Guo Wengui, who threatened to reveal corruption at the country's highest levels.
Authorities in China and Hong Kong have accused Guo, a real estate tycoon who resides in the United States, of laundering billions of dollars among other crimes.