Development of new wheat cultivars combining good local adaptation, disease resistance and grain quality represents an important strategy component for national food security. Uzbekistan was identified by N. Vavilov as important center of wheat diversity. An inventory of landraces was conducted in 2010–2013 in western Tien-Shan Mountains to survey, collect, and characterize old wheats still grown by farmers. Thirty landraces were collected from 17 villages in Jizzakh, Kashkadarya and Surkhandarya Regions. The material went through spike selection, head-rows, un-replicated trials in Tashkent, Uzbekistan (2012–2015), and replicated trials in Konya, Turkey (2018–2019). Landrace diversity was described using spike morphological traits and DNA profiles as reflected by single nucleotide polymorphism. A socioeconomic survey demonstrated that wheat landraces are grown in remote mountain communities by subsistence farmers despite having access to modern cultivars, and both are frequently grown together. The main reasons for the maintenance of landraces are: (1) large grain with excellent bread-making quality and suitability for home-baking; (2) specific adaptations allowing stable and reliable yield; and (3) straw yield and quality. Similar genomic profiles shared by some landraces from remote regions of Uzbekistan and neighboring Tajikistan demonstrated their common origin and are indicative of seed exchange between farmers. Agronomic characterization demonstrated the resilient nature of their adaptation based on spring and facultative growth habit and superiority of some landraces for grain yield and its components compared to local checks. Viable options for maintaining and expanding on-farm wheat diversity include their improvement through selection and breeding, market development, variable incentives, and capacity building. For the first time, this paper presents results of a unique 10-year study in Uzbekistan on social conditions in the areas where wheat landraces are grown, analyses the diversity of these landraces, evaluates agronomic characteristics, and discusses the sustainability options for on-farm wheat landraces use and conservation.