The Ministry of Health has confirmed first two cases of the deadly Marburg virus, a highly infectious disease in the same family as the virus that causes Ebola.
It says both patients died recently in hospital in the southern part Ashanti region.
Their samples came back positive earlier this month and have now been verified by a laboratory in Senegal.
The Ghana Health Service says about 98 people are now under quarantine as suspected contact cases.
No treatment yet exists for Marburg – but doctors say drinking plenty of water and treating specific symptoms improves a patient’s chances of survival.
The virus is transmitted to people from fruit bats and spreads between humans through the transmission of bodily fluids.
It is a severe, often fatal illness with symptoms including headache, fever, muscle pains, vomiting blood and bleeding.
Officials are warning people to keep away from caves and to thoroughly cook all meat products before consuming them.
In Africa, previous outbreaks and sporadic cases have been reported in Angola, Democratic Republic of the Congo, Kenya, South Africa and Uganda, the WHO says. The first ever Marburg outbreak was in Germany in 1967 where seven people died.
The virus killed more than 200 people in Angola in 2005, the deadliest outbreak on record according to the global health body.