Lexical inference strategy plays an important role in increasing the level of reading comprehension of second or foreign language learners. Lexical inferencing as an efficient strategy to deal with unfamiliar words has attracted much attention in the comprehension literature. However, few studies on lexical inferencing have been conducted in an English as a foreign language (EFL) setting. To fill in the existing gap, the current study aimed at investigating the effect of lexical inferencing strategy instruction on Saudi EFL students' reading comprehension. Additionally, it sought to identify the lexical inferencing strategies used by Saudi EFL learners while they were inferring unknown words in a text. Last, the current study attempted to find the relationship between lexical inference strategies and reading comprehension among Saudi EFL learners. Sixty students from the English department were selected based on their scores on the Oxford Placement Test, indicating that they were at intermediate levels of English proficiency. The participants were randomly divided into two groups: control and experimental (each consisting of 30 students). The participants in the control group received regular instruction, while the participants in the experimental group were treated using lexical inference strategies. The instruments used for collecting data were Oxford Placement Test, reading comprehension test, and think-aloud protocol. A pre-test and post-test were administered for control and experimental groups. The results of the independent samples t-test revealed that teaching inference skills had a significant effect on reading comprehension performance among EFL learners. The results of the paired t-tests showed that lexical inferencing instruction had a statistically significant effect on EFL learners' reading comprehension development. The results of the Spearman correlation coefficient indicated that there was a significant relationship between lexical inferencing strategies and reading comprehension. The findings revealed the profound impact of lexical inferencing strategy instruction on the experimental group's performance in understanding reading text. Hence, it was concluded that lexical inferencing strategies were recommended to teach to improve the students' reading comprehension performance.