Dr Tedros Adhanom Ghebreyesu warned against "narrow nationalism and vaccine hoarding" in a new year statement.
His comments come two years since the WHO was first notified of cases of an unknown pneumonia strain in China.
Global Covid cases now stand at 287m, while nearly 5.5m people have died.
Across the world people are marking the new year but celebrations are muted, with many countries wanting to discourage crowds gathering.
Coronavirus remains part of daily life: a disease that has shut borders, split families and in some places made it unthinkable to leave the house without carrying a mask.
Despite all this, Dr Tedros sounded a positive note in his speech, noting that there are now many more tools to treat Covid-19.
But he warned that continuing inequity in vaccine distribution was increasing the risk of the virus evolving.
"Narrow nationalism and vaccine hoarding by some countries have undermined equity and created the ideal conditions for the emergence of the Omicron variant, and the longer inequity continues, the higher the risks of the virus evolving in ways we can't prevent or predict," he said.
"If we end inequity, we end the pandemic," he added.