The effective design of course materials is critical for student learning, especially for large lecture introductory courses. This quantitative study was designed to explore the effect multimedia and content difficulty has on students' cognitive load and learning outcomes. College students (n = 268) were randomized into 1 of 3 multimedia groups: text + graphics (Group 1-TG); audio + text + graphics (Group 2-ATG); or video + audio + text + graphics (Group 3-VATG). Participants answered a demographic survey and pretests before viewing 2 food science supplemental lecture materials (i.e., water mobility and amino acid structures) and completing the cognitive load instrument and post-tests within a noncontrolled setting. Cognitive load scores were tabulated and compared using a 3 × 3 ANOVA and Tukey post hoc analysis across multimedia groups and food science supplemental lecture materials. Based on the post hoc, students in Group 1-TG had higher intrinsic cognitive load scores than Group 2-ATG (ANOVA, P < 0.05). Cognitive load and post-test scores were tabulated and compared using a spearman correlation across groups. In Group 1-TG, students that reported less intrinsic cognitive load had higher post-test scores. Also, students that reported more germane cognitive load had higher post-test scores. In Groups 2-ATG and 3-VATG, students that reported less extraneous cognitive load had higher post-test scores (ANOVA, P < 0.05).