Grandin was born in St. Pierre-la-Coeur, France, on 23 April 1829. He was ordained as a priest in 1854; one month later he was sent by the Missionary Oblates of Mary Immaculate to Canada to perform missionary work in what was then Rupert's Land. Upon arrival he was sent to Saint-Boniface, where Bishop Alexandre-Antonin Taché was in charge. Grandin was subsequently assigned to a mission at Fort Chipewyan (now in Alberta). He next served at Île-à-la-Crosse (now in Saskatchewan) for a number of years.
In 1867, Taché proposed that the vicariate of Saskatchewan be formed with Grandin as vicar of missions. This took place in 1868; in the same year, Grandin attended the council of Quebec bishops in 1868 to discuss new religious boundaries in the Canadian northwest. As a result of these discussions, St. Boniface was elevated and the suffragan diocese of St. Albert was created. In 1871, Vital-Justin Grandin was appointed bishop.
Grandin was never completely healthy; he had been a sickly child and also had a speech impediment, and his health deteriorated during his later years. He did however preside over the development and expansion of the Diocese of St. Albert, including the founding of new missions and churches throughout Alberta and the construction of hospitals and schools which, unusually for the time, were administered by members of female religious orders and lay clergy. Grandin's efforts to increase Francophone settlement in Alberta were less successful, but many francophone communities founded at the behest of Grandin (such as Beaumont, Lacombe, and Morinville) still exist in central and Northern Alberta.
Upon his death, Grandin was succeeded by Bishop Émile-Joseph Legal in the St. Albert diocese.