He was born at Caen. After completing his studies in Paris, he was appointed by Cardinal Richelieu inspector of the printing-press at the Louvre. After Richelieu's death he left Paris, joined the Reformed Church, and in 1651 obtained a professorship at the academy of Saumur, which he filled with great success for nearly twenty years. His increasing ill-health and a certain moral laxity (as shown in his judgment on Sappho) led to a quarrel with the consistory, as a result of which he resigned his professorship. Several universities were eager to obtain his services, and he had accepted a post offered him by the elector palatine at Heidelberg, when he died suddenly. One of his children, Anne, became famous as Madame Dacier.
Lefebvre was a highly cultivated man and a thorough classical scholar. He brought out editions of various Greek and Latin authors: Longinus, Anacreon and Sappho, Virgil, Horace, Lucretius and many others.
His most important original works are: Les Vies des poètes Grecs (1665); Méthode pour commencer les humanités Grecques et latines (2nd ed., 1731), of which several English adaptations have appeared; and Epistolae Criticae (1659).
In addition to the Mémoires pour ... la vie de Tanneguy Lefebvre, by F. Graverol (1686), see the article in the Nouvelle biographie générale, based partly on the manuscript registers of the Saumur Académie.