Polyploidy was induced in Melia volkensii (Mukau), a valuable native tree from the semi-arid regions of East Africa. Cotyledons of diploid M. volkensii (2n = 2x = 28) were treated with oryzalin for 0 (control), 1, 2, or 3 h with or without pretreatment with 1.1 µM thidiazuron. Cotyledons treated with 10 mg·L−1 oryzalin for three hours yielded 40% tetraploids. Pretreatment of cotyledons with thidiazuron for 18 days followed by treatment with oryzalin increased tetraploid plant production to 52.5%, but this also yielded more mixoploids. Compared to diploid M. volkensii, the tetraploid in vitro and young potted plants were compacter, with thicker stems, wider leaves, and a low density of longer and wider stomata. In the coming years, tetraploid M. volkensii plants will be observed in field trials and serve as a basis for further breeding efforts.