Subsidence curves for Cambrian-Ordovician sequences from the Anglo-Welsh segment of the paleocontinent of Avalonia reveal two periods of regionally enhanced basement subsidence: Early Cambrian (545–518 Ma) and Late Cambrian to early Tremadocian (505–490 Ma). The earlier event may record transtension following the Avalonian-Cadomian orogeny. The second event may be a transtensional precursor to the late Tremadocian volcanic arc on Eastern Avalonia. However, paleomagnetic, faunal, volcanic, and sedimentary evidence suggests that the main separation of Eastern Avalonia from Gondwana occurred after middle Arenigian time. Rifting during separation is probably recorded by localized middle Arenigian to Llanvirnian (480–462 Ma) subsidence along the Welsh basin margin, but rifting must have occurred mainly on the now-obscured southern margin of the Avalonian continent. Pronounced Caradocian (462–449 Ma) subsidence is associated with back-arc rifting after separation from Gondwana.