The study is aimed at investigating the effects of four learning methods on students' scientific inquiry skills. The four learning methods are: (a) metacognitive-guided inquiry within asynchronous learning networked technology (MINT); (b) an asynchronous learning network (ALN) with no metacognitive guidance; (c) metacognitive-guided inquiry embedded within face-to-face (F2F) interaction; and (d) F2F interaction with no metacognitive guidance. The study examined general scientific ability and domain-specific inquiry skills in microbiology. Participants were 407 10th-grade students (15 years old). The MINT research group significantly outperformed all other research groups, and F2F (group d) acquired the lowest mean scores. No significant differences were found between research groups (b) and (c). MINT makes significant contributions to students' achievements in designing experiments and drawing conclusions. The novel use of metacognitive training within an ALN environment demonstrates the advantage of enhancing the effects of ALN on students achievements in science.