This study (1) explores the effectiveness of the contextualized history of science on student learning of nature of science (NOS) and genetics content knowledge (GCK), especially interrelationships among various genetics concepts, in high school biology classrooms; (2) provides an exemplar for teachers on how to utilize history of science in genetics instruction; and (3) suggests a modified concept mapping assessment tool for both NOS and GCK. A quasi-experimental control group research design was utilized with pretests, posttests, and delayed posttests, combining qualitative data and quantitative data. The experimental group was taught with historical curricular lessons, while the control group was taught with non-historical curricular lessons. The results indicated that students in the experimental group developed better understanding in targeted aspects of NOS immediately after the intervention and retained their learning 2 months after the intervention. Both groups developed similar genetics knowledge in the posttest, and revealed a slight decay in their understanding in the delayed posttest.