The Appalachians was just the first of a series of mountain building plate collisions that contributed to the formation of the Appalachians. Mountain building continued periodically throughout the next 250 million years (Caledonian, Acadian, Ouachita, Hercynian, and Allegheny orogenies. Continent after continent was thrust and sutured onto the North American craton as the Pangean supercontinent began to take shape. Microplates, smaller bits of crust, too small to be called continents, were swept in, one by one, to be welded to the growing mass. By about 300 million years ago (Pennsylvanian Period) Africa was approaching North American craton. The collisional belt spread into the Ozark-Ouachita region and through the Marathon Mountains area of Texas. The massive bulk of Pangea was completed near the end of the Paleozoic Era (Permian Period ) when Africa (Gondwana) plowed into the continental agglomeration, with the Appalachian-Ouachita mountains near the core.

During the Late Devonian, the Antler orogeny is a mountain-building episode that is named for Antler Peak, at Battle Mountain, Nevada. The orogeny extensively deformed Paleozoic rocks of the Great Basin in Nevada and western Utah during Late Devonian and Early Mississippian time. In the late Devonian, the Antler volcanic island arc, approaching the west coast of North America, which was a passive margin with deep embayments, river deltas and estuaries, in today's Idaho and Nevada, finally reached the steep slope of the continental shelf and began to uplift deep water deposits. Colliding Antler terrane shoved sediments that had been deposited in deep water over the continental shelf to form the Antler orogeny. Minor orogenic pulses followed the main event, extending into the Permian. It is broadly contemporary with the Acadian orogeny of eastern North America during middle Paleozoic deformation.

Akin to the London-Brabant Massif, As the continent drifted northwards, away from the Equator, through the latitudes represented today by the Sahara desert, the erosion was renewed. This time, the lateritic soils are represented by the New Red Sandstone and the red soils of Leicestershire and Rutland during the Permian and Triassic. The early Permian was the time of the height of the Variscan earth movements as the crust to the south was crushed against the island. The great disturbances seen at the surface in Brittany, the Ardennes and the Rhineland also lie below the Paris Basin. The period from which the island has exercised most influence on modern Europe was the Carboniferous. As the continent was drifting past the Equator, on the island's shores, there grew a rich tropical forest swamp. On the island's southern shore, it left the Dinantian / Avonian (Lower Carboniferous), Namurian and Westphalian coal fields of France and Belgium. To its north-west, it left those of Leicestershire and Nottinghamshire. By the Cretaceous the island had sunk much further in relation the sea level. Before the end of the period, the British end was buried in Upper Cretaceous chalk.

The Variscan or Hercynian orogeny is a geologic mountain-building event recorded in the European mountains and hills called the Variscan Belt. This occurred in Paleozoic times (from ~390 to ~310 mya) and reflects continental collision between Laurasia and Gondwana to form Pangea, much less Tethys Ocean. This early collision was a precursor to the collision that caused the Variscan-Allegheny-Ouachita orogeny in Pennsylvanian times. The Variscan orogeny is sometimes also known as the Amorican orogeny. The European Variscan Belt (also called Variscides) includes the mountains of Portugal and western Spain, south-western Ireland, Cornwall, Pembrokeshire, the Gower peninsula and the Vale of Glamorgan. Its effects are present in France from Brittany, below the Paris Basin to the Ardennes, the Massif Central, the Vosges and Corsica as shows in Sardinia in Italy and in Germany where the Hunsrück, the Black Forest and Harz Mountains remain as testimony.

The Variscan was contemporaneous with the Acadian orogeny in the United States, which raised the Appalachian Mountains; then continuous with the Caledonides, the mountains raised by the Caledonian orogeny. The Caledonian orogeny is a mountain building event recorded in the mountains and hills of northern England, Wales, Scotland, Ireland and west Norway. This event occurred during the Silurian and Devonian Periods of the Palaeozoic Era, roughly 444-416 Mya. During the Mesozoic Era, the existence of a supercontinent, Pangaea, in which most of the land mass was conjoined into a single large continent surrounded by a single large ocean, Panthalassa.

The Caledonian range already existed and was contiguous to the ancestor of the Appalachian Mountains of the eastern United States.

The origin of the Caledonian range occurred earlier, during the assembly of Pangaea by the convergence of more ancient plates. In the preceding Ordovician Period, ca. 488-444 Mya, the largest continent, Gondwana, containing the plates of the future Africa, South America, and Antarctica, was located between the South Pole and the Equator. To the northeast was the Siberian Plate, separated from Gondwana by the Palaeotethys Ocean; to the southeast, the Baltic Plate, or Baltica, separated from Gondwana by Iapetus Ocean. In the Iapetus Ocean was a long archipelago, Avalonia, containing New England, Nova Scotia and the British Isles. It was divided from Gondwana by an oceanic rift.

In the Ordovician Period, the rift began to open, pushing Baltica and Avalonia in the direction of Laurentia by sea-floor spreading. Baltica and northern Avalonia collided first, causing the Caledonian Origeny of the Silurian. At the end of the Silurian and in the subsequent Devonian, the rest of Avalonia collided, causing the Acadian Orogeny of North America, which raised the early Appalachian Mountains. By the end of the Silurian, seafloor spreading to the south of Avalonia had pushed the latter into north Laurentia, creating the Caledonide mountains. In the succeeding Devonian, the Iapetus Ocean between Avalonia and Laurentia entirely closed, joining the two masses and thrusting up the northern Appalachians in the Acadian orogeny.

The Variscan belt was in place by the early Carboniferous. By the end of the Carboniferous, Gondwana had united with Laurentia. Siberia was approaching from the northeast, separated from Laurentia only by shallow waters. Collision with Siberia produced the Ural Mountains in the latest Paleozoic. In the Triassic Period of the Mesozoic Era, animals could move without oceanic impediment from Siberia over the North Pole to Antarctica over the South Pole. This traversability especially assisted the spread of the mobile Dinosaurs. In the Cenozoic Era, Laurasia divided from Gondwana, while Siberia with Baltica split from Laurentia. As a consequence, the Variscan Belt around then periphery of Baltica ended up many hundreds of miles from the Appalachians.