Background: Different instructional factors are related to students’ achievement in different cognitive domains. Most research studies on large-scale assessment focus on science achievement as an entire variable, without considering science achievement in different cognitive domains. Purpose: This study investigates the predictive effects of the frequency of teachers’ using practical work and clarity of instruction on students’ achievement in different cognitive domains. Sample: A regional representative sample of 3265 Hong Kong students who took part in Trends in International Mathematics and Science Study (TIMSS) 2019 was used in this study. Design and Method: In order to disentangle the interrelationships between science instructional factors, attitudes toward science and students’ achievement in different cognitive domains, we carried out structural equation modelling to explore the responses by 3265 Hong Kong students to TIMSS 2019 surveys. Results: Frequency of teachers’ use of practical work had a significant positive impact on students’ achievement in the domains of knowing, applying, and reasoning, while clarity of instruction had a significantly negative impact on students’ achievement in the domains of knowing and applying. Enjoyment of science mediates the relationship between the relationships between frequency of practical work and achievement in three cognitive domains. Conclusion: This informs how teachers use practical work to enhance students’ enjoyment of science, intrinsic motivation and self-concept, in order to improve their achievement in knowing, applying and reasoning science. Implications contribute to future research on how best to improve students’ achievement in all three cognitive domains are discussed. Copyright © 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.