Ug99 is a lineage of wheat stem rust (Puccinia graminis f. sp. tritici), which is present in wheat fields in several countries in Africa and the Middle East and is predicted to spread rapidly through these regions and possibly further afield, potentially causing a wheat production disaster that would affect food security worldwide. In 2005 the noted green revolution pioneer Norman Borlaug brought great attention to the problem, and most subsequent efforts can be traced to his advocacy. It can cause up to 100% crop losses and is virulent against many resistance genes which have previously protected wheat against stem rust.

Although Ug99-resistant varieties of wheat do exist, a screen of 200,000 wheat varieties used in 22 African and Asian countries found that only 5–10% of the area of wheat grown in these countries consisted of varieties with adequate resistance.

The original race of Ug99, which is designated as 'TTKSK' under the North American nomenclature system, was first detected in Uganda in 1998 and first characterised in 1999 (hence the name Ug99) and has since been detected in Kenya, Ethiopia, Eritrea, Sudan, Yemen, Iran, Tanzania, Mozambique, Zimbabwe, South Africa, and Egypt. There are now 15 known races of Ug99. They are all closely related and are believed to have evolved from a common ancestor, but differ in their virulence/avirulence profiles and the countries in which they have been detected.

Ug99 is the product of a type of somatic nuclear exchange event which has not been observed in other stem rust races. During this event and thereafter the nuclei have not experienced recombination.

Ug99 and its variants differ from other strains of the Black Stem Rust (BSR) pathogen due to their ability to overcome resistance genes in wheat that have been durable against the BSR pathogen for decades. These resistant Sr genes, of which 50 are known, give wheat different resistances to stem rust. The virulence in Uganda was virulent against Sr31 and is specific to Ug99. The massive losses of wheat that have occurred have been devastating, but in recent years the wheat rust epidemic has been effectively controlled through selection and breeding for additional Sr genes. (In the decades since, however, Sr31-virulence has evolved in other strains in other locations. Patpour et al., 2022 finds it in Spain and Siberia.)

United States Department of Agriculture (USDA) researchers are testing genes to determine their Ug99 resistance, which will ultimately aid in the development of wheat varieties that will be able to fight off the rust. Resistance has been identified in a small number of spring wheat land races from North America – 23 out of 250 races with adult plant resistance, 27 out of 23,976 SNPs conveying APR, and only 9 races having seedling resistance. This resistance was present without the Ug99 pathogen challenge being present in NA to drive its selection. USDA has studied winter wheat land races where resistance is more probable.

In addition to the research being conducted by the USDA, The United Kingdom's Department for International Development (DFID) along with Bill & Melinda Gates Foundation, announced in February 2011 that they will be granting $40 million to a global project led by Cornell University to combat virulent strains of Ug99. The five-year grant to the Durable Rust Resistance in Wheat (DRRW) project supported attempts to identify new resistance genes as well as reproduce and distribute rust resistant wheat seeds to farmers.

There has been a continuous process of development of new resistant cultivars and failure of those cultivars. This demonstrates the need for continuous improvement.