Transportation and spatial planning are inextricably linked. Transport networks and facilities have an immense influence on the spatial development of any city. Moreover, they determine the nature of the neighbourhood and the quality of life by directly influencing property market values. Transit-oriented development seeks to integrate urban spaces and bring people, amenities, and activities together with easy cycling and walking proximities to the excellent transit services. Consequently, successful transportation and spatial planning integration result in efficient transit-oriented development. This paper presents pathways for enhancing sustainable mobility and access through transit-oriented development networks in South African Cities. The paper adopts a case study research design wherein the impact of transit-oriented developments in the City of Johannesburg is presented and discussed. Quantitative and qualitative research approaches were deployed to gather relevant data, as well as specific questionnaires and interview guides. Preliminary findings reveal that transit-oriented developments have tremendous benefits and effectively transform neighbourhoods. There are still challenges associated with and hindering the integration of transit-oriented development and spatial planning in the City of Johannesburg. The paper concludes by recommending cities in South Africa and other developing countries adopt and implement transit-oriented development to achieve sustainable cities concerning efficient physical connectivity, mobility, and accessibility and to ensure climate-friendly and liveable cities. Lastly, transit-oriented development must be crystallised in city-wide developments in order to overcome contemporary mobility and access challenges in cities of the Global South.