This study describes the cytogenetic characteristics of 7,133 trisomy 21 (Tri21) identified from 247,818 consecutive postnatal cases karyotyped in a single reference laboratory in China for a period of 4 years. The average detection rate of Tri21 is 2.88% ranging from 3.39% in 2011 to 2.52% in 2014. The decreased detection rates over the years might reflect a possible impact of noninvasive prenatal testing applied rapidly in China and elective termination of affected pregnancies. 95.32% of the Tri21 karyotypes are standard Tri21, 4.53% are Robertsonian Tri21, and less than 1% are other Tri21 forms. There are more mosaic Tri21 in older children and adults, consistent with previous observations that clinical features in individuals with mosaic Tri21 are generally milder and easily missed during perinatal period. The male/female (M/F ratio) for the total 7,133 Tri21 cases and for the 6,671 cases with non-mosaic standard Tri21 are 1.50 and 1.53 respectively, significantly higher than the 0.93 for all the 247,818 cases we karyotyped, the 1.30 for the Down syndrome (DS) identified during perinatal period in China, and the 1.20 for the livebirth in Chinese population. In contrast, the mosaic standard Tri21 case has a significantly lower proportion of males when compared with the non-mosaic standard Tri21, indicating different underlying mechanisms leading to their formations. Opposite M/F ratios in different subtypes of ROB Tri21 were observed. A long list of rare or private karyotypes where Tri21 are concurrently present was identified. The large collection of Tri21 cases with a diversity of clinical findings and a wide age range allowed us to determine the frequency of the different karyotypes of Down syndrome in China, given the fact that this kind of national epidemiological data is lacking currently.