This paper presents a study on the interactive roles of lexical knowledge and reading strategies on reading comprehension performance of ESL learners. It examines how the lexical knowledge or the reading strategies contribute to second language (L2) reading comprehension. It also investigates whether there is a relationship among the three main variables which are lexical knowledge, reading strategies and reading comprehension performance. The Survey of Reading Strategy (SORS), the Vocabulary Levels Test, a writing test and a reading comprehension test were administered to 70 students from the Public Administration Course through convenience sampling method. Descriptive statistics was used to describe the participants’ performance on the three tests and their reading strategies used as well as to assess the relationship between the three main variables of this study. On the whole, the participants reported using most of the reading strategies with high and moderate frequencies. Apart from that, it is found that, the students’ word mastery level is only 2,000 word families, which is far below the minimum level required for tertiary education. There is no correlation found between the reading strategies used and the reading comprehension achievement of the participants. On the other hand, a statistically significant relationship (r= .739, p<0.01) was found between the participants vocabulary size and reading comprehension performance. The findings of this study help both language teachers and students to acknowledge the roles of lexical knowledge and reading strategies in improving the L2 reading comprehension performance. Keywords: Global strategies, lexical knowledge, problem-solving strategies, reading strategies, support strategies. Cite as: Zuriyani, M. Y. & Mohamed Ismail, A. S. (2019). The interactive roles of lexical knowledge and reading strategies on reading comprehension performance. Journal of Nusantara Studies, 4(1), 273-299. http://dx.doi.org/10.24200/jonus.vol4iss1pp273-299