ABSTRACT: Importance:In Africa, the persistently high HIV incidence rate among young women is the major obstacle to achieving the goal of epidemic control. Objective:To determine trends in coverage of HIV prevention and treatment programs and HIV incidence. Design, Setting, and Participants:This cohort study consisted of 2 sequential, community-based longitudinal studies performed in the Vulindlela and Greater Edendale area in KwaZulu-Natal, South Africa. Participants enrolled from June 11, 2014, to June 22, 2015 (2014 survey), with a single follow-up visit from June 24, 2016, to April 3, 2017 (2016 cohort), or enrolled from July 8, 2015, to June 7, 2016 (2015 survey), with a single follow-up visit from November 7, 2016, to August 30, 2017 (2017 cohort). Men and women aged 15 to 49 years were enrolled in the 2014 and 2015 surveys, and HIV-seronegative participants aged 15 to 35 years were followed up in the 2016 and 2017 cohorts. Analysis was conducted from January 1 through December 31, 2018. Exposures:HIV prevention and treatment programs in a real-world, nontrial setting. Main Outcomes and Measures:Trends in sex- and age-specific HIV incidence rates, condom use, voluntary medical male circumcision, knowledge of HIV-seropositive status, uptake of antiretroviral therapy, and viral suppression. Results:A total of 9812 participants (6265 women [63.9%]; median age, 27 years [interquartile range, 20-36 years]) from 11 289 households were enrolled in the 2014 survey, and 10 236 participants (6341 women [61.9%]; median age, 27 years [interquartile range, 20-36 years]) from 12 247 households were enrolled in the 2015 survey. Of these, 3536 of 4539 (annual retention rate of 86.7%) completed follow-up in the 2016 cohort, and 3907 of 5307 (annual retention rate of 81.4%) completed follow-up in the 2017 cohort. From 2014 to 2015, condom use with last sex partner decreased by 10% from 24.0% (n = 644 of 3547) to 21.6% (n = 728 of 3895; P = .12) in men and by 17% from 19.6% (n = 1039 of 6265) to 16.2% (n = 871 of 6341; P = .002) in women. Voluntary medical male circumcision increased by 13% from 31.9% (1102 of 3547) to 36.1% (n = 1472 of 3895); P = .007) in men, and the proportion of women reporting that their partner was circumcised increased by 35% from 35.7% (n = 1695 of 4766) to 48.2% (n = 2519 of 5207; P < .001). Knowledge of HIV-seropositive status increased by 21% from 51.8% (n = 504 of 3547) to 62.9% (n = 570 of 3895; P < .001) in men and by 14% from 64.6% (n = 1833 of 6265) to 73.4% (n = 2182 of 6341; P < .001) in women. Use of antiretroviral therapy increased by 32% from 36.7% (n = 341 of 3547) to 48.6% (n = 432 of 3895; P < .001) in men and by 29% from 45.6% (n = 1251 of 6265) to 58.8% (n = 1743 of 6341; P < .001) in women; HIV viral suppression increased by 20% from 41.9% (n = 401 of 3547) to 50.3% (n = 456 of 3895; P = .005) in men and by 13% from 54.8% (n = 1547 of 6265) to 61.9% (n = 1828 of 6341; P < .001) in women. Incidence of HIV declined in women aged 15 to 19 years from 4.63 (95% CI, 3.29-6.52) to 2.74 (95% CI, 1.84-4.09) per 100 person-years (P = .04) but declined marginally or remained unchanged among men and women in other age groups. Conclusions and Relevance:This study showed a significant decline in HIV incidence in young women; however, to further reduce HIV incidence, HIV prevention and treatment program coverage must be intensified and scaled up.