Research has shown that context cue instruction can improve EFL learners’ ability to infer word meanings from context, improve their comprehension and enable them to read independently (Nash & Snowling, 2006; Yuen, 2009; Çetinavci, 2013; Dwaik et al., 2013; and Samiyan et al., 2014). However, this strategy has not been explicitly taught in the context of secondary schools in Vietnam, and language learners are assumed to learn the strategy on their own. Therefore, this study was conducted to find out the extent to which context cue instruction enhances learners’ ability to infer word meanings from context and to investigate learners’ perceptions towards this strategy. In this study, 26 English major eleventh graders in an upper-secondary school in Can Tho City, Vietnam, were instructed to guess meanings of unfamiliar words using the contextual guessing strategy in three three-hour sessions. Achievement tests and learners’ reflection done in class were employed as sources of quantitative and qualitative data. Data from the pre-tests and post-tests indicated a significant improvement in learners’ ability to guess meanings of unfamiliar words using the contextual guessing strategy. Results of twenty-six reflections also showed positive perceptions towards using this strategy. It could be implied that secondary school teachers should train and encourage learners to guess meanings of unknown words based on the contextual cues, and integrate context cue instruction into reading lesson plans to help strengthen learners’ ability to infer word meaning from context.