Rwigema was born in Gitarama, in the south of Rwanda. Considered an ethnic Tutsi, he and his family fled to Uganda and settled in a refugee camp in Nshungerezi, Ankole in 1960 following the so-called Hutu Revolution of 1959 and the ouster of King Kigeri V.
After finishing high school in 1976, he went to Tanzania and joined the Front for National Salvation (FRONASA), a rebel group headed by Yoweri Museveni, the brother of his friend Salim Saleh. It was at this point that he began calling himself Fred Rwigema. Later that year, he travelled to Mozambique and joined the FRELIMO rebels who were fighting for the liberation of Mozambique from Portugal's colonial power
After the NRA captured state power in 1986, Rwigyema became the deputy Minister of Defence. He was regularly at the front line in northern Uganda during the new government's offensives against remnants of the ousted regime.