King Mibambwe III Mutabazi Sentabyo, like his predecessors, co-reigned with his father. After his father's death, he was enthroned at Gasange near Lake Muhazi, in the former Giti commune, now Giti sector in Gicumbi district (1741-1746). His reign was short-lived, marked by significant opposition.

Upon his enthronement, Sentabyo faced resistance, particularly from Gatarabuhura, who believed he was the rightful heir to the throne. Another contender, Rukali, also attempted to claim the throne but failed. After his scheme failed, Rukali tried to flee but was intercepted and thrown into Lake Muhazi as punishment.

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Dynastic poets, including Muganza, chronicled these rivalries. Muganza's poem, "Ntawe urenga icyo azira,” emphasized that no one has the right to rebel against a divinely chosen king.

Gasenyi, one of King Kigeli III Ndabarasa's sons, also opposed Sentabyo. He fled to Gisaka after failing to gain support for his schemes. The poet Musare told him in a poem that a throne is inherited, not usurped, reflecting the belief that esoteric codes, not individual ambition, determined the rightful ruler. Despite these challenges, Prince Semugaza, a powerful militia commander, posed a latent threat but did not openly oppose Sentabyo.

A plot to assassinate King Sentabyo was orchestrated by Gatarabuhura from his hiding place. The king's intelligence network foiled the plot, apprehending the would-be assassin, Rubaba. Instead of executing Rubaba, Sentabyo pardoned him, sending him to join his cohorts in Gisaka.

Gatarabuhura continued his schemes from Gisaka, sending Ruhogo to Rwanda under the guise of seeking forgiveness. Despite being pardoned and settled by the king, Ruhogo attempted to assassinate Sentabyo with an arrow but failed. The king ordered his fingers cut off and sent to the border as a warning.

Gisaka continued to harbor those opposing Sentabyo. This prompted plans to attack Gisaka, and Kanywabahizi was chosen as the liberator. However, Kanywabahizi betrayed the king and joined the conspirators in Gisaka. Semucumisi was then chosen to replace him, as recounted in a poem by Musare, son of Karimunda.

While Rwanda was preparing to attack Gisaka, a smallpox epidemic broke out there. Fearing the epidemic would spread to Rwanda, Sentabyo retreated to Remera in Kamonyi district, decreeing that no one cross the Nyaborongo eastwards to prevent the spread of the disease.

King Kimenyi Getura of Gisaka, fearing a Rwandan invasion, supported Gatarabuhura's cohort. He hatched a plot, sending a pretender to Rwanda with a gift of leather clothing infected with smallpox.

This ploy succeeded where others had failed, and King Sentabyo died of smallpox after wearing the clothing. His relatives and only son from a Ndorwa woman also perished.

King Sentabyo was buried at Ku Rurembo (Nyansenge) in Rutare sector, now in Gicumbi district.