The 15th to 18th centuries were marked by economic (trade and agriculture) and cultural development (the construction of monasteries and churches) and population growth.

In 1812, after the Russo-Turkish War (1806-1812), the Russian Empire occupied Basarabia; during the period 1812–1917, there was an intense russification of the native population.

In 1918, after the collapse of the Russian Empire, Bessarabia united with Romania; during this period (1918–1940, 1941–1944), Nisporeni District was part of Chisinau County.

In 1991, as a result of the independence of Moldova, Nisporeni District became part of Ungheni County (1991–2003); in 2003, it became a separate administrative unit.

The hilly landscape is fragmented by valleys 150 to 250 metres (490 to 820 ft) deep, with steep ravines which develop landslides.

In the western part of the Codri is the highest point in Moldova, Bălănești Hill, at a height of 430 metres (1,410 ft).

Nisporeni District, in common with the republic, has a temperate continental climate with mild, short winters and warm, long summers.

The Prut, which crosses the district in the west, borders Romania; its principal tributaries are the Nîrnova and the Lăpușna.

Land in production makes up 21,736 hectares (83.92 sq mi) (34.5 percent of total land area) as follows: Principal crops include grapes, cereals (wheat and oats), orchards (peach, apple and plum), sunflowers and rapeseed.