The earliests roots of the domaine goes back to 1717 and a Claude Leflaive in Puligny-Montrachet. The domaine of today more directly goes back to Joseph Leflaive (1870–1953), who was a native of Puligny-Montrachet, but who had initially pursued a career as a naval engineer, having managed a factory in St Etienne and been involved in the construction of the first French submarine. In 1905, when Burgundy had not yet recovered from the effect of the phylloxera epidemic, which meant that vineyards were for sale at a very low price, Leflaive was able to buy 25 hectares (62 acres) for his domaine.
In 1920, Leflaive started a programme of replantation with better adapted root stock, and progressively started to sell wine under his own label rather than to négociants. After the death of Joseph Leflaive in 1953, the domaine was managed by Joseph's sons Vincent Leflaive and Jo Leflaive, and it was during this time that its reputation as a top Burgundy producer was built up. In 1973, the domaine was given a company structure to avoid splitting it up with subsequent inheritance. In 1990, Vincent's daughter Anne-Claude Leflaive and her cousin Olivier Leflaive took over the running of the domain. Because Olivier Leflaive was also running a négociant business, in 1994, Anne-Claude Leflaive took over the running of the domain on her own, following a decision of the various family members who collectively own the domaine. In 1997, Anne-Claude took the decision to convert the domain to biodynamic winemaking.
Domaine Leflaive and Olivier Leflaive's négociant business are completely separate entities.