The association between vocabulary knowledge and reading comprehension has been extensively researched. However, modeling the contribution of vocabulary knowledge within different frequency ranges to second language (L2) learners' reading comprehension is an underexplored area. Thus, the present study examines the degree to which high-, mid-, and low-frequency-based levels of orthographic vocabulary knowledge are able to predict L2 reading comprehension. A vocabulary size test and the reading section of International English Language Testing System (IELTS) were administered to 256 tertiary-level Arab learners of English. The participants' language proficiency ranged from B2 to C1 of Common European Framework of Reference (CEFR) levels. Results showed that high- and mid-frequency word ranges contributed uniquely to the L2 reading comprehension for the entire cohort. When the participants were categorized to relatively low- and relatively high-proficiency subgroups, only high-frequency range explained variance in L2 reading comprehension for the low-proficiency subgroup. Among the high-proficiency subgroup, high-, mid-, and low-frequency-based ranges offered unique contribution to L2 reading comprehension, but mid-frequency range explained the largest variance. The findings provide evidence aimed at informing approaches to the development of overall vocabulary size and the mid-frequency words, and not just a focus on the most frequent vocabulary, for the purpose of supporting L2 reading comprehension.