Structures in Phanerozoic rocks along the southwestern margin of the intracratonic Illinois basin vary in deformational styles and orientations. These variations have been inherited from the Proterozoic basement. Based on them, a tectonic framework is developed that divides the margin into three tectonic domains separated by two northeast-trending zones of accommodation. Both zones of accommodation are interpreted as major Proterozoic crustal boundaries that have partitioned strain throughout the Phanerozoic. Each tectonic domain has a distinct neotectonic and seismic history, which is also attributable to strain partitioning along the zones of accommodation. The northern tectonic domain constitutes part of the Mississippi River arch, which lies north of St. Louis, Missouri. This arch separates the northern part of the Illinois basin from the Forest City basin to the west and contains faulted, asymmetrical anticlines and monoclines that have high structural relief, and broad anticlines and synclines that have low structural relief. Structural trends range from north-northwest to west-northwest. These structures underwent multiple Paleozoic deformations but have been mostly inactive since the late Paleozoic. There are few suggestions of any neotectonic activity in this domain and very little seismicity during the past 25 years. The northeast-trending St. Charles lineament (SCL) is a zone of accommodation that separates the northern and central tectonic domains. The SCL coincides with an extensive Proterozoic crustal boundary as defined by Nd geochemistry, across which basement rocks of differing lithologies and ages are juxtaposed. This crustal boundary is interpreted as a possible ancient transform fault. Locally, strike-slip faulting occurred along the SCL, probably in the late Paleozoic. Possible neotectonism occurred along the SCL, as well as some recent light to very minor seismicity. The central tectonic domain lies between the two zones of accommodation and contains complex fault systems that trend prominently northwest. Geologic mapping and structural analysis document a complex history of episodic left-lateral strike-slip and reverse faulting during the Paleozoic. Some of these faults may be branches of a deeply rooted flower structure in the crust and may have influenced the emplacement of ultramafic diatremes in the Devonian. Neotectonic features are localized in the southern part of this domain. Recorded seismicity is scattered throughout the central tectonic domain, but is more concentrated in the southeastern half. The Commerce geophysical lineament (CGL) is a northeast-trending feature that extends from northeastern Arkansas to at least Vincennes, Indiana. It is a zone of accommodation between the central and southern tectonic domains. This feature has been interpreted to consist of en-echelon faults and igneous intrusions in the basement that are related to the Neoproterozoic to early Paleozoic Reelfoot rift; however, it is postulated to have an even older ancestry. In the Thebes Gap area of Missouri and Illinois, a well developed system of northeast-to-north-northeast-trending, strike-slip faults occurs directly over the CGL. These faults cut Paleozoic, Mesozoic, and Cenozoic formations and have had a long-lived and episodic tectonic history, including Pleistocene and Holocene activity. In the past 25 years, several dozen light to minor earthquakes ( mb 2-4) have occurred on, or adjacent to, the CGL. The southern tectonic domain is roughly equivalent to the northern Mississippi embayment and contains many northeast-trending faults related to the Reelfoot rift. This domain also contains the New Madrid seismic zone, the most seismically active area east of the Rocky Mountains and the site of historical great earthquakes. During the late Paleozoic, uplift of the broad northwest-trending Pascola arch, which directly overlies the Mesoproterozoic Missouri batholith, closed the southwestern margin of the Illinois basin from its connection to the Arkoma basin. This uplifted arch extends across the central and southern tectonic domains and is partitioned also by the CGL. We propose a model in which the New Madrid seismic zone is a descendant of similar, intense, late Paleozoic tectonism that was concentrated in the southern domain at the intersection of the Pascola arch and the Reelfoot rift.