Firefighters are battling two uncontrolled bushfires, one at Dimboola and Wail near the South Australian border and the other in the southwestern part of the Grampians National Park.
The Dimboola fire was sparked by dry lightning at Little Desert National Park on Monday and has already grown to 63,000 hectares, State Control Centre spokesperson Luke Heagerty said.
It's too late for residents to leave, with anyone left in the town urged to take shelter immediately.
"The fire grew to such a size and was carrying such energy with it yesterday that it made it quite difficult for any containment to occur," Mr Heagerty told AAP.
A popular wedding and conference centre, Little Desert Nature Lodge, was destroyed in the blaze, Hindmarsh Shire Council mayor Ron Ismay confirmed.
He's been told a firefighter on the ground said the venue and some surrounding accommodation in the wildlife reserve went up very quickly.
"The lodge just exploded, it's totally gone," Mr Ismay said.
"It's very sad, it was a great venue for people of the area, and it was used for weddings and conferences and meetings and all sorts of stuff.
"So it's a big loss to the community".
Premier Jacinta Allan said there have been no deaths in the fires but confirmed the property losses at the Little Desert Nature Lodge.
"The commissioner advised me that the main building and a number of cabins have been lost at that facility," Ms Allan told reporters in Werribee.
Mr Heagerty said it appears the fire spread from public land to private property near the Wimmera River, close to the Dimboola Golf Course.
It's believed most residents had evacuated to Horsham while it was still safe, and it's not yet known if any homes were lost.
"Assessments for property impacts will start today once there's some better light in the area, and it's safe for our crews to do so," he said.
An additional 25 fire trucks were sent to attack that fire, with embers sparking small blazes ahead of the main blaze.
A second emergency warning has been issued for Strachans, Victoria Point and Victoria Valley in the Grampians National Park, in an area that has a mix of private property and campsites.
The area was not impacted by fires at the Grampians earlier this summer, with holidaymakers and residents now told to evacuate while it's still safe to do so.
Mr Heagerty said it's expected crews would be battling the fires for several weeks, and authorities are concerned there may be other fires they do not yet know about.
"We can also have scenarios where dry lightning starts a fire in a tree stump, for example, it might not show up for another week or two," he said.
A cool change swept through Victoria after Monday's dry, gusty conditions however Mr Heagerty said crews are still expecting "variable" conditions for the rest of Tuesday.
Fires have been burning across the Grampians region since mid-December.
Ms Allan said there were up to 150 fires across the state as high heat and winds brought dangerous conditions and fire bans.
With AAP.
