The Mesozoic–Cenozoic convergent margin history of southern Alaska has been dominated by arc magmatism, terrane accretion, strike-slip fault systems, and possible spreading-ridge subduction. We apply 40Ar/39Ar, apatite fission-track (AFT), and apatite (U-Th)/He (AHe) geochronology and thermochronology to plutonic and volcanic rocks in the southern Talkeetna Mountains of Alaska to document regional magmatism, rock cooling, and inferred exhumation patterns as proxies for the region’s deformation history and to better delineate the overall tectonic history of southern Alaska. High-temperature 40Ar/39Ar thermochronology on muscovite, biotite, and K-feldspar from Jurassic granitoids indicates postemplacement (ca. 158–125 Ma) cooling and Paleocene (ca. 61 Ma) thermal resetting. 40Ar/39Ar whole-rock volcanic ages and 45 AFT cooling ages in the southern Talkeetna Mountains are predominantly Paleocene–Eocene, suggesting that the mountain range has a component of paleotopography that formed during an earlier tectonic setting. Miocene AHe cooling ages within ∼10 km of the Castle Mountain fault suggest ∼2–3 km of vertical displacement and that the Castle Mountain fault also contributed to topographic development in the Talkeetna Mountains, likely in response to the flat-slab subduction of the Yakutat microplate. Paleocene–Eocene volcanic and exhumation-related cooling ages across southern Alaska north of the Border Ranges fault system are similar and show no S-N or W-E progressions, suggesting a broadly synchronous and widespread volcanic and exhumation event that conflicts with the proposed diachronous subduction of an active west-east–sweeping spreading ridge beneath south-central Alaska. To reconcile this, we propose a new model for the Cenozoic tectonic evolution of southern Alaska. We infer that subparallel to the trench slab breakoff initiated at ca. 60 Ma and led to exhumation, and rock cooling synchronously across south-central Alaska, played a primary role in the development of the southern Talkeetna Mountains, and was potentially followed by a period of southern Alaska transform margin tectonics.