In 1852 his studies took him to London and Paris. In 1854 he became a teacher at a Berlin public school, but this did not interrupt his biblical studies. He edited the Didascalia apostolorum syriace (1854) and other Syriac texts collected in the British Museum and in Paris. In 1866 he received three years leave of absence to collect fresh materials, and in 1869 succeeded Heinrich Ewald as professor of oriental languages at Göttingen.
Like Ewald, Lagarde was an active worker in a variety of subjects and languages; but his chief aim, the elucidation of the Bible, was almost always kept in view. He edited the Aramaic translation (known as the Targum) of the Prophets according to the Codex Reuchlinianus preserved at Carlsruhe, Prophetae chaldaice (1872), the Hagiographa chaldaice (1874), an Arabic translation of the Gospels, Die vier Evangelien, arabisch aus der Wiener Handschrift herausgegeben (1864), a Syriac translation of the Old Testament Apocrypha, Libri V. T. apocryphi syriace (1865), a Coptic translation of the Pentateuch, Der Pentateuch koptisch (1867), and a part of the Lucianic text of the Septuagint, which he was able to reconstruct from manuscripts for nearly half the Old Testament. Lagarde was easily the most renowned Septuagint scholar of the nineteenth century.
He devoted himself ardently to oriental scholarship, and published Zur Urgeschichte der Armenier (1854) and Armenische Studien (1877). He was also a student of Persian, publishing Isaias persice (1883) and Persische Studien (1884). He followed up his Coptic studies with Aegyptiaca (1883), and published many minor contributions to the study of oriental languages in Gesammelte Abhandlungen (1866), Symmicta (1. 1877, ii. 1880), Semitica (i. 1878, ii. 1879), Orient alia (1879-1880) and Mittheilungen (1884). Mention should also be made of the valuable Onomastica sacra (1870; 2nd ed., 1887).
Lagarde's anti-Semitism laid the foundations for aspects of National Socialist ideology, in particular that of Alfred Rosenberg. He argued that Germany should create a "national" form of Christianity purged of Semitic elements (see Positive Christianity) and insisted that Jews were "pests and parasites" who should be destroyed "as speedily and thoroughly as possible".
He died at Göttingen.