Orthophragminids are larger benthic foraminifera (LBF) and, together with the nummulitids, were the major rock-forming foraminifera from the middle Paleocene to the late Eocene. Today, porous, LBF-bearing, Paleogene limestones, which occur globally from the Pacific and Atlantic margins of the Americas to the Indo-Pacific, form potentially valuable oil reservoirs, and their biota have formed the basis of the definition of three paleobiogeographic provinces, namely those of the Americas, Tethys, and the Indo-Pacific. The orthophragminids of the western part of the Tethyan Province have been studied extensively, however, the other provinces are less well characterized, and until now the origin and paleogeographic development of this group have not been fully articulated. New material described here allows the clear definition of a fourth, South African paleobiogeographic province, and, when combined with refined biostratigraphic dating based on new material from the Americas, Europe, South Asia and SE Asia, enables their paleogeographic and biostratigraphic evolution to be determined. Critically, the occurrence of cosmopolitan planktonic foraminifera (PF) within LBF assemblages enables the first occurrences of various LBF forms within each province to be dated relative to well-calibrated planktonic zones (PZ). From this, we infer that, like the previously studied lepidocyclinids and nummulitids, the orthophragminids originated in the Americas during the Paleocene, probably between the late Danian (PZ P1c, 63.5 Ma) and the early Selandian (PZ P3a, 61.6 Ma). By the middle Paleocene, the orthophragminids had migrated across the Atlantic to the previously isolated West African coast at the extreme of Tethys, probably during global sea-level low stands at 60.3 Ma and again at 56.4 Ma. Subsequently, the American Province again became isolated. In the Tethys, the orthophragminid migrations followed two paths: northeastward through the Tethyan corridor in the late Paleo-cene (Thanetian), and south in the earliest Eocene (Ypresian) to South Africa. The Tethyan forms evolved during the Eocene into many lineages, which in turn migrated, after a few million years of their first appearances into the Indo-Pacific, where they again became isolated and diversified further. Meanwhile the South African forms remained similar to their American ancestors in both small size and external ornamentation, while their internal evolution closely followed that of Tethys forms, as exhibited by three species of Nemkovella and Discocyclina described here from South Africa (Nemkovella mcmilliana n. sp., Discocyclina davyi n. sp. and D. africana n. sp.).