Zimbru Chișinău was formed in 1947 in the Moldovan Soviet Republic (present day Republic of Moldova). 'Zimbru' is a Romanian word for a form of European bison, but the club also previously functioned under names such as Dynamo, Burevestnik, Moldova, Avântul, and Nistru. The Soviet Era was spent mostly in Class B of the regional league until eventual promotion to Class A. The club then flitted between Class A and Class B as well as spending time in the Soviet Top League and First League. In total, Zimbru spent 11 seasons in the Top League between 1956 and 1983. Zimbru had their biggest success in 1956 when they finished in 6th place out of 12 in the Soviet Top League and in 1963 when they reached the quarter-finals of the Soviet Cup.
Zimbru's fortunes changed after the fall of the USSR and the establishment of the Republic of Moldova. The club won all five of the initial seasons of the Moldovan National Division (1992–96), and apart from finishing as runners-up to Chișinău rivals Constructorul Chișinău in 1996–97, won eight of the first nine championships. Zimbru have also won the Moldovan Cup six times, including a double in 1997–98 and the Moldovan Super Cup in 2014. Zimbru's biggest rivalry is with Sheriff Tiraspol, who in the last eighteen years have won sixteen championships.
In the 1990s (the first decade of Moldova's independence), Zimbru's rival was the other team from Chișinău, Constructorul Chișinău. Then Contructorul was dissolved. In 1997, a new team was founded in Tiraspol, Sheriff Tiraspol. In a few years, Sheriff was promoted to the first league and became a force in Moldovan football. Considering the strength of team and the tensions between Moldovans and separatist Transnistrians, the match between Zimbru and Sheriff became a derby, the most important match in country. Thus, it has been named "Derby of Moldova". Another rivalry was established in the mid 2000s when Dacia Chișinău, another team from Chișinău, became one of Moldova's top teams. Zimbru also has a rivalry with Olimpia Bălți.