Background: Morphological analysis skill is the ability to problem-solve meanings of unfamiliar words by applying knowledge of morphological constituents. For vocabulary words from the academic layer of English, the major, meaning-carrying morphological constituents are Latin roots (nov meaning 'new' in innovative). The degree to which morphological analysis skill using Latin roots is susceptible to intervention and whether improvements relate to reading comprehension remains unclear. Methods: We investigated the effects of a morphology intervention designed to promote academic vocabulary learning, morphological analysis and reading comprehension with 140 adolescent, multilingual learners in US schools (intervention n = 70; comparison n = 70). We estimated direct effects of the intervention on morphological analysis and academic vocabulary knowledge and examined whether they mediate intervention effects on reading comprehension. Academic vocabulary was measured as both definitional and multidimensional knowledge. Results: We found significant, direct effects of the intervention on morphological analysis skill and academic vocabulary knowledge. Additionally, we found a significant indirect effect on reading comprehension via academic vocabulary and a marginally significant indirect effect via morphological analysis skill. Notably, the indirect effect of academic vocabulary was evident only for multidimensional, not definitional knowledge. Conclusions: Findings extend current understanding about how morphology intervention promotes vocabulary and reading comprehension improvement for multilingual learners.