Genetics has been identified as one of the difficult topics in biology for high school students in Zambia. This paper reports a study conducted to determine the nature and causes of learning difficulties students encounter in genetics at high school level in Zambia. A survey design was used and data were obtained from students and teachers using interview schedules and self-completion questionnaires. Quota sampling procedure was used to select the sample from the target population. Data collected were analysed using content analysis approach. The study found that students had difficulties understanding among others genetic crosses, genetic terms, mitosis and meiosis as well as mutation. Factors identified to have caused learning difficulties included: inability by teachers to explain clearly to students; none teaching of the topic; topic taught near examination time, fast presentation of lessons by some teachers; belief by some students that genetics was difficult to learn; lack of appropriate learning aids and inadequate time allocated to teaching of the topic. Some of the recommendations made were that: teacher training institutions must prepare biology teachers adequately to teach this topic well; adequate time should be allocated to teaching of genetics; teachers need in-service training to enable them use appropriate teaching methods for teaching genetics.