Strong winds - gusting up to 100km/h in some areas - have grounded helicopters trying to respond.
People are being advised to follow emergency service instructions and leave their houses as soon as possible.
Otago Rural Fire Authority spokesman Jamie Cowan said the two largest fires were at Saddle Hill and in Dunback, near Palmerston.
In Mosgiel, about 25 properties were in the process of being evacuated after fire broke out near Coal Stage Rd about 1.30pm.
"We are currently working with the police and are in the process of multiple evacuations as the fire is immediately threatening houses and is out of control," said Mr Cowan.
Six fire appliances and two helicopters are on site, he said.
Chain Hills Rd resident Gordon Hunt said police were advising residents in the road to start packing bags and prepare to leave their homes.
Several people were watching the fire from the intersection of Chain Hills Rd and Morris Rd and the heat was intense.
"The heat from the motorway was horrendous."
Dunedin Police Senior Sergeant Brian Benn said a house was on fire, and residents were being evacuated from Coal Stage Rd and McMaster Rd.
Police are diverting traffic in the area.
Hundreds of people will be without power for an unknown period of time as a result of the fire, said Aurora Energy capability and risk manager Matt Ballard.
Aurora reported an outage in the East Taieri shortly before a fire outbreak was announced at Saddle Hill, which Mr Ballard said has "escalated as the fire situation's developed".
He said the outage and the fire "could be related, but we won't know until the source of the fire is understood".
At Dunback, a fire started about 6.25am and was 4km long and uncontrollable, said Mr Cowan.
By this afternoon, the blaze has moved rapidly towards houses on the Dunback-Palmerston Rd, which has been closed.
Five properties had been evacuated and there was three helicopters and nine fire appliances on site.
"That fire if out of control and we are currently carrying out structure protection up there," said Mr Cowan.
"We are not fighting the fire, it's un-fightable at the moment so we are focussing solely on the properties."
Mr Cowan said the fires were being caused by wind and low humidity.
"There are several fires throughout Otago caused mainly by the very, very high winds gusting up to 100km/h.
"We also very low humidity, under 20 per cent in some areas, which is particularly low for this time of year."
Winds were dropping, but it was expected that fire crews would work throughout the night to control the blazes.
New Zealand Transport Authority has advised of a number of fire and wind cautions throughout the South Island.
The Otago Regional Council has issued an advisory saying buses will be delayed and their routes altered due to the fire.
'It's raining quite hard, so hopefully that is going to help
Mosgiel resident Francis Murphy said his old farm was one of the properties on fire.
He had planted most of the trees at the property - a farm on Coalstage Rd - but sold it when he retired last year and moved into the Fairfield township.
"It's quite serious, we are not far away from the fire - just down the road a bit.
"There is still a lot of smoke around and all the roads are blocked off, all I can see from here is just a bit of the hill and from the skyline the rest is smoke."
Mr Murphy said the winds were dropping and it had started to rain about 4.30pm.
"It's raining quite hard, so hopefully that is going to help."