Down syndrome or Down's syndrome, also known as trisomy 21, is a genetic disorder caused by the presence of all or part of a third copy of chromosome 21. It is usually associated with developmental delays, mild to moderate intellectual disability, and characteristic physical features. There are three types of Down syndrome, all with the same features: Trisomy 21, the most common type; Mosaic Down syndrome, and Translocation Down syndrome.

The parents of the affected individual are usually genetically normal. The probability increases from less than 0.1% in 20-year-old mothers to 3% in those of age 45. The extra chromosome is provided at conception as the egg and sperm combine. A very small percentage of 1-2% gets the additional chromosome in the embryo stage and it only impacts some of the cells in the body; this is known as Mosaic Down syndrome. Usually, babies get 23 chromosomes from each parent for a total of 46, whereas in Down syndrome, a third 21st chromosome is attached. It is believed to occur by chance, with no known behavioral activity or environmental factor that changes the probability. Down syndrome can be identified during pregnancy by prenatal screening, followed by diagnostic testing, or after birth by direct observation and genetic testing. Since the introduction of screening, Down syndrome pregnancies are often aborted (rates varying from 50%-85% depending on maternal age, gestational age, and maternal race/ethnicity).

There is no cure for Down syndrome. Education and proper care have been shown to provide good quality of life. Some children with Down syndrome are educated in typical school classes, while others require more specialized education. Some individuals with Down syndrome graduate from high school, and a few attend post-secondary education. In adulthood, about 20% in the United States do paid work in some capacity, with many requiring a sheltered work environment. Support in financial and legal matters is often needed. Life expectancy is around 50 to 60 years in the developed world, with proper health care. Regular screening for health issues common in Down syndrome is recommended throughout the person's life.

Down syndrome is the most common chromosomal abnormality. It occurs in about 1 in 1,000 babies born each year. In the US this figure is given as one in 700 births. In 2015, Down syndrome was present in 5.4 million individuals globally and resulted in 27,000 deaths, down from 43,000 deaths in 1990. It is named after British doctor John Langdon Down, who fully described the syndrome in 1866. Some aspects of the condition were described earlier by French psychiatrist Jean-Étienne Dominique Esquirol in 1838 and French physician Édouard Séguin in 1844. The genetic cause of Down syndrome was discovered in 1959.