Objective: To investigate sexual behavior changes adopted by People Living with Human Immunodeficiency Virus (PLHIV) on Antiretroviral therapy (ART) in the Northern Region of Ghana. Methods: We employed a cross-sectional survey with a questionnaire to collect data from 900 clients from 9 major ART centers within the region. Chi-square and logistic regression analyses were applied to the data. Results: More than 50% of PLHIV on ART use condoms, reduce sexual partners, practice abstinence, reduce unprotected sex with married/regular partners, and avoid casual sex. Fear of others getting to know patients’ HIV-positive status (χ2= 7.916,p= 0.005), stigma (χ2= 5.201,p= 0.023), and fear of loss of family support (χ2= 4.211,p= 0.040) significantly predict non-disclosure of HIV-positive status among the participants. Change in sexual behavior is influenced by the following: “to avoid spreading the disease to others” (R2= 0.043,F(1, 898) = 40.237,p< 0.0005), “to avoid contracting other STIs” (R2= 0.010,F(1, 898) = 8.937,p< 0.0005), “to live long” (R2= 0.038,F(1, 898) = 35.816,p< 0.0005), “to hide HIV-positive status” (R2= 0.038, F (1, 898) = 35.587,p< 0.0005), “to achieve good results from ART treatment” (R2= 0.005,F(1, 898) = 4. 282,p< 0.05), and “to live a Godly life” (R2= 0.023,F(1, 898) = 20. 880,p< 0.0005). Conclusions: High self-disclosure rate of HIV-positive status was identified, with participants disclosing to their spouses or parents. Reasons for disclosure and non-disclosure differed from person to person.