AS of 6pm tonight, masks will be compulsory for all indoor public settings in the Wheatbelt and Great Southern regions.
The mask rule will also apply to anyone who has been in these regions since January 20 and has since travelled to another region.
It comes as more COVID-19 cases and exposure sites are being detected outside of the Perth, Peel and South-West regions and concerns of further cases being identified in the coming days.
Masks must be worn in all indoor public settings, including in vulnerable settings such as aged care facilities and hospitals - usual exemptions apply.
Premier Mark McGowan said what has been seen with cases in regional WA is concerning and it's known that Omicron doesn't respect regional boundaries.
"Third dose vaccinations and mask wearing help limit the spread of Omicron, which is why masks will be mandatory for all public indoor settings in the Wheatbelt and Great Southern," Mr McGowan said.
"Just like in Perth, Peel and the South-West, it's important to follow this public health rule now, to slow the spread of Omicron in the regions.
"I urge all Western Australians, no matter where they live, to do the right thing, to protect yourselves, your loved ones and the wider community."
This public health rule is in addition to the mask-wearing mandate currently in place for Perth and Peel, and the South-West.
All measures will be reviewed regularly and the Chief Health Officer will continue to monitor the serious situation.
The mask mandate may need to be extended to other regions in the future.
The Department of Health is working through reported cases and is in the process of identifying close and casual contacts, and additional exposure sites.
Health Minister Amber-Jade Sanderson said it is time for people in the Wheatbelt or the Great Southern to protect themselves by wearing a mask while at public venues indoors.
"We now have three confirmed cases of COVID-19 in this region and I'd encourage people to take this seriously," Ms Sanderson said.
"Please check the exposure sites often as they are being regularly updated and get tested.
"If you haven't already please get vaccinated, including your third dose, when you are due."
People are asked to check the exposure sites list regularly and monitor their health and get tested immediately, and self-quarantine, if they develop symptoms.