This descriptive survey research aimed to identify the topics within Senior Secondary (SS) I – II biology curriculum perceived as difficult by SS II students and biology teachers. The population comprised 27,375 SS II students and 209 biology teachers in Zamfara State. The sample size of 378 students were sampled using random sampling technique, while 48 biology teachers having minimum of 5 years of teaching experience were purposively selected. An instrument titled Difficult Biology Topics Scale with reliability coefficients of 0.82 was used for data collection. Two research questions and one null hypothesis guided the study. Mean and standard deviation were used to answer the research questions while the hypothesis was tested using t-test at 0.05 level of significance. The findings revealed that, in all the listed 30 biology topics, SS II students and their teachers identified Nutrition in animals, Respiratory system, and Pests and diseases of crops as difficult. More so, SS II students identified the topic Cell and its environment, Functioning ecosystems, and Nutrient cycle as difficult, while teachers considered them easier. The disparity in perceived difficulty levels of 30 biology topics between SS II students and teachers was statistically significant (t=2.51, df=424, p=0.030). The study recommends targeted professional development for biology teachers and use of student-centered approaches in remediating the perception that some biology topics are difficult.