Nine previously unreported phragmalin-type limonoid orthoesters, named ivorenoids G-O (1-9), together with seventeen known analogues (10-26) were isolated from the twigs and leaves of Khaya ivorensis. Their structures, including absolute configurations, were determined by extensive spectroscopic analyses, electronic circular dichroism calculations, and single-crystal X-ray diffraction. Selected compounds were evaluated for cytotoxicity against five human cancer cell lines (HL-60, A-549, SMMC-7721, MCF-7, and SW480), and their structure-activity relationships were systematically analyzed. Notably, compound 15 exhibited cytotoxicity against A549 and SMMC-7721 cell lines, with IC50 values of 14.0 ± 0.4 μM and 14.9 ± 0.6 μM, respectively. Compound 22 showed cytotoxicity against SW480 cells, with an IC50 value of 7.5 ± 0.2 μM, while compound 25 displayed cytotoxicity against A549 cells, with an IC50 of 14.6 ± 1.9 μM. These findings highlight the potential of limonoid orthesters derived from K. ivorensis as promising lead compounds for further anticancer drug development.