"I encourage all countries to become party to the treaty. This can result in millions of lives saved, and that is where the real success of this treaty resides," said WHO Director General Lee Jong Wook.
"Its entry into force is a demonstration of governments' commitment to reduce death and illness from tobacco use," he added.
The WHO regards tobacco as the only legal product that eventually kills half its regular users, fuelling the second leading cause of death in the world.
"This means that out of 1.3 billion smokers, 650 million will die prematurely," it added in a statement.
Tobacco-related ill health is thought to sap 200 billion dollars from rich and poor countries.
The cost of treating illness due to smoking is estimated to rise to 6.5 billion dollars in China alone, according to the UN's health agency.
Despite three years of strong opposition from tobacco multinationals, as well as governments with substantial tobacco industries or farming, the treaty concluded in 2003 advocates bans on advertising and sponsorship, as well as sales to minors.
The Framework Convention on Tobacco Control also includes public smoking restrictions, larger health warnings on cigarette packs and promotes taxation as a way to cut consumption and fight smuggling.
Treaty parties must now pass the measures into national law within three to five years, although health officials acknowledged that several countries have already implemented many of them.