Introduction: Oxygen is essential in healthcare for treating respiratory diseases and emergencies. Its availability can prevent significant deaths, particularly in low-income countries. Effective oxygen therapy protocols improve patient outcomes and enhance nurses' knowledge and practice. Methodology: The study evaluated the effectiveness of demonstrations on knowledge and practice regarding oxygen therapy among first-year nursing students using a true experimental pre-test post-test design. Conducted at a nursing institute with 100 students (50 in the experimental and 50 in the control group), the study employed a quantitative approach. Participants included second-semester B.Sc. Nursing and first-year General Nursing and Midwifery students, selected via simple random sampling. Data collection involved a semi-structured questionnaire for demographics, a self-administered questionnaire for knowledge assessment, and an observation checklist for practical skills. Reliability of the tools was confirmed with the Karl Pearson correlation coefficient for the questionnaire (0.983) and the Parallel form method for the checklist (0.9914), both exceeding the acceptable threshold of 0.8. Result: The study assessed the impact of a demonstration on oxygen therapy knowledge and practice among first-year nursing students by comparing pre-test and post-test scores in both experimental and control groups. The experimental group showed notable improvements: their knowledge score increased from a pre-test mean of 8.36 (SD = 3.15) to a post-test mean of 18.86 (SD = 3.19), with a mean difference of 10.50 ± 4.16. In contrast, the control group's knowledge score changed slightly, from a pre-test mean of 7.86 (SD = 2.14) to a post-test mean of 7.08 (SD = 2.07), resulting in a mean difference of 0.78 ± 2.50. Practice scores for the experimental group also improved significantly, from a pre-test mean of 6.34 (SD = 2.70) to a post-test mean of 22.84 (SD = 4.41), with a mean difference of 16.50 ± 4.33. The control group showed minimal change. Statistical analysis with unpaired t-tests revealed significant improvements for the experimental group, with t-values (23.257 and 22.177) exceeding the critical value of 1.984, demonstrating the effectiveness of the intervention. Conclusion: The intervention significantly improved both knowledge and practice of oxygen therapy in first-year nursing students, with the experimental group showing marked gains over the control group. Statistical analysis confirmed the effectiveness of the demonstration.