Background: Cognitive and linguistic factors have been incorporated into models to explain reading comprehension beyond classical models of reading. This study explores the contribution of executive functions, mainly domain-general and reading-specific cognitive flexibility, in reading comprehension of science texts in monolingual Spanish speaking upper elementary students. Methods: A total of 275 Chilean students from fourth to sixth grade participated in this study. They were evaluated in working memory, inhibition, reading fluency, domain-general and reading-specific cognitive flexibility, academic vocabulary and science reading comprehension. Results: The results show that cognitive flexibility is a variable that explains performance in science reading comprehension across elementary grades. Furthermore, reading domain-specific cognitive flexibility was found to be the variable that explains additional performance in science reading comprehension above inhibition, reading fluency, academic vocabulary and domain-general cognitive flexibility in Grade 4 and Grade 5, but not in Grade 6. Conclusions: These results suggest the contribution of cognitive variables such as cognitive flexibility in explaining performance in reading comprehension of science texts. The need to develop cognitive tests specific to reading domain is also discussed.