The study identified and analyzed the learning difficulties experienced in chemistry by senior secondary two (SS2) students in Awka Education Zone of Anambra State. Five research questions guided the study and three null hypotheses were tested at 0.05 level of significance. The design of the study was descriptive survey. Purposive sampling technique was used to select a sample size 450 from a population of 4,206 Chemistry students in the study area. Chemistry Learning Difficulty Assessment Questionnaire (CLDAQ) was used to collect data on types of learning difficulties, factors responsible for learning difficulties and ways of overcoming learning difficulties in Chemistry. The CLDAQ was validated by three experts from Nnamdi Azikiwe University, Awka. The reliability coefficients of 0.81, 0.78, 0.87 and 0.71 were found for clusters A to D respectively and an overall reliability index of 0.79 using Cronbach Alpha formula. Mean and standard deviation were used to answer the research questions while two-way ANOVA was used to test the null hypotheses. The findings of the study revealed among others that chemistry students experience difficulty in mathematical aspect of chemistry which are dyscaculia difficulty and attention/concentration difficulty. However, there is significant difference between learning difficulties in chemistry experienced by male and female students; male students experience difficulty more than females among others. Based on the findings of the study, it was recommended among others that relevant authorities like curriculum planners, policy makers, Government, school administrators and Professional Association like STAN should organize seminars, conferences and workshops for pre-service and in-service teachers, and chemistry students from time to time in order to equip them with skills and strategies in teaching and learning of chemistry to reduce or eliminate these difficulties.