The purpose of this study was to compare the 5E method of inquiry-based instruction (IBI) and the four-stage model of direct instruction (DI) on students' content knowledge achievement. The population for this study was all secondary high school students enrolled in the CASE® Natural Resources and Ecology course and whose teachers completed the CASE® Institute for Natural Resources and Ecology certification between the years 2013 and 2017. This study was quasi-experimental and used a nonequivalent control group, pretest-posttest design. A convenient sample of 13 teachers and 222 students was collected. Each teacher was randomly assigned to deliver a set of 16 lesson plans that utilized either the IBI or DI approach. Lesson plans were grouped into four modules, each lasting approximately two weeks. Prior to the delivery of each module, teachers administered content knowledge pretests. Posttests were administered at the completion of each 2-week module. Students in both groups demonstrated significant gains in content knowledge achievement. ANCOVA statistical procedures were used to compare student achievement for both instructional methods. Results of the ANCOVA indicated that the 5E method of IBI and the four-stage model of DI are equally effective on students' content knowledge achievement.