According to Morning Star News, the group entered the home of Mamwikomba Mwanika in Kalampete village, in the eastern Kibuku District, declaring their intention to murder her husband George.
George Mwanika had been debating with Islamic scholars and sharing the Good News of Jesus Christ with Muslim locals.
When Mamwikomba said George was not present, she was dragged from her house and murdered around 100 metres away. Two of her daughters, aged 9 and 11, were in the house when events occurred.
Mr Mwanika came back to find his wife alive in a pool of blood, but she died on the way to hospital. She leaves eight children.
He said: "I know that the attackers are looking for me. We are seeking God's protection and His peace.
"May God give me the courage to continue sharing the love of Christ to those who are lost, as Jesus said we should love our enemies.
"We really need prayers."
Other incidents of persecution against Christians have happened in Uganda this year.
Jafalan Kadondi and her son Ibrahim Kasoono were beaten to death in August for converting from Islam to Christianity, while Namumbeiza Swabura was poisoned to death when she and her husband converted in June.
A mob also gang-raped a pastor's 17-year-old daughter in March.
Around 85 percent of Uganda's population are Christians, however believers can be a minority in some eastern parts of the country.