This study aims to enhance understanding of the factors underlying variance in the reading comprehension skills of prelingually deaf individuals. Participants were 213 sixth through tenth graders with prelingual deafness recruited from four orthographic backgrounds (Hebrew, Arabic, English, and German) and allocated to three distinct reading profiles (levels). A sentence comprehension test manipulating the semantic plausibility of sentences and a word processing experiment requiring rapid determination of the semantic relationship between two real words or between a real word and a pseudohomophonic letter string were used to determine the factors distinguishing skilled from less skilled deaf readers. Findings point to deficits in structural (syntactic) knowledge and deficient knowledge structures, rather than differences in phonological processing skills, as making that distinction. Moreover, the acquisition of such knowledge seems to be modified by particularities of the read orthography.