The relationship between motivation and the use of learning strategies is a focus of research in order to improve students’ learning. Meaningful learning requires a learner’s personal commitment to put forth the required effort needed to acquire new knowledge. This commitment involves emotional as well as cognitive and metacognitive factors, and requires the ability to manage different resources at hand, in order to achieve the proposed learning goals. The main objectives in the present study were to analyse: (a) Spanish secondary school students’ motivation and self-perception of using strategies when learning science; (b) the nature of the relationship between motivation and perceived use of learning strategies; (c) the influence of different motivational, cognitive, metacognitive and management strategies on students’ science achievement. The Motivated Strategies for Learning Questionnaire (MSLQ) was administered to 364 middle and high-school students in grades 7–11. For each participant, the academic achievement was provided by the respective science teacher. The results obtained from the Pearson product-moment correlations between the study variables and a stepwise regression analysis suggested that: (1) motivation, cognitive and metacognitive, and resource management strategies, have a significant influence on students’ science achievement; (2) students’ motivation acts as a kind of enabling factor for the intellectual effort, which is assessed by the self-perceived use of learning strategies in science; and, (3) motivational components have a greater impact on students’ performance in science than cognitive and metacognitive strategies, with self-efficacy being the variable with the strongest influence. These results suggest a reflexion about the limited impact on science achievement of the self-perceived use of cognitive and metacognitive strategies, and highlight the importance of students’ self-efficacy in science, in line with previous studies.