Dr Tedros Adhanom Ghebreyesus cautioned against the assumption that the newly dominant Omicron variant is significantly milder and has eliminated the threat posed by the virus.
The intervention comes as some European nations saw record new case numbers.
Speaking during a news conference at the WHO's headquarters in Geneva, Dr Tedros told reporters that the Omicron variant had led to 18 million new infections across the world over the past week.
While the variant may prove to be less severe on average, "the narrative that it is a mild disease is misleading," he said. "Make no mistake, Omicron is causing hospitalisations and deaths, and even the less severe cases are inundating health facilities."
He warned global leaders that "with the incredible growth of Omicron globally, new variants are likely to emerge, which is why tracking and assessment remain critical".
The WHO's emergencies director, Dr Mike Ryan, also warned that Omicron's increased transmissibility is likely to drive a rise in hospitalisations and deaths, especially in nations where fewer people are vaccinated.
Cases rise in Europe
New coronavirus infections have been growing across Europe as the new Omicron variant takes hold across the continent.
In Denmark, officials reported a record 33,493 new daily cases of Covid-19 on Tuesday, while health authorities in Italy recorded 228,179 new infections, up from 83,403 the previous day.
In Germany a record 112,323 new cases were reported on Wednesday, and the incidence rate of cases per 100,000 people also climbed to a new high of 584.4 over the past week. This is the first time since the start of the pandemic, that more than 100,000 new infections were recorded in Germany within 24 hours.
France meanwhile reported 464,769 new daily infections on Tuesday, more than four times higher than Monday's figure of 102,144 and a daily record for the pandemic. Infections have now climbed past a weekly average of over 300,000 new cases per day.
In Ireland new cases have started to fall in recent days, with health minister Stephen Donnelly telling public broadcaster RTÉ that restrictions introduced over Christmas and the New Year period could be loosed by the end of the month.
Spanish government data has shown that new infections have started to fall for first time since the Omicron wave began two and a half months ago - although experts warned about reading too much into the data.
Italy reported 228,179 coronavirus cases on Tuesday. That compares with 83,403 cases a day earlier, according to the health ministry. There were 434 Covid-linked deaths, almost a 50% increase from the 287 logged on Monday.
In the UK, government ministers are set to review coronavirus restrictions on Wednesday amid a decline in daily infections.
US
The Omicron variant has pushed the country’s daily case reports to record levels, with more than 800,000 new infections being reported each day.
Most of the country continues to see explosive case growth, but infection levels seem to have peaked in some of the places that were hit first by Omicron.
Australia
Australia on Tuesday suffered its deadliest day of the pandemic as a fast-moving Omicron outbreak continued to push up hospitalisation rates to record levels, even as daily infections eased slightly.
Australia has reported about 1.6 million infections since the pandemic began, of which around 1.3 million were in the last two weeks. Total deaths stood at 2,757.
India
India reported 2.82 lakh new Covid cases, 441 deaths in last 24 hours. Active cases in India now stands at 18,31,000; Omicron tally at 8,961.
India’s Covid-19 vaccination coverage exceeds 158.88 crore
China
China on Tuesday reported 55 new locally-transmitted Covid-19 cases amid the emergence of the Omicron Covid-19 variant cases in the country. According to Xinhua News Agency, out of the new local cases, 33 infections were reported in Henan, 14 in Tianjin, seven in Guangdong, and one in Beijing, the National Health Commission said on Wednesday.