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The role of lithospheric heterogeneities, presence or absence of melt, local and regional stresses, and gravitational potential energy in strain localization in continental rifts remains debated. We use new seismic and geodetic data to identify the location and orientation of the modern Nubia‐Somalia plate boundary in the 300‐km‐wide zone between the southern Main Ethiopian Rift (MER) and Eastern Rift (ER) across the Mesozoic Anza rift in the Turkana Depression. This region exhibits lithospheric heterogeneity, 45 Ma‐Recent magmatism, and more than 1,500 m of base‐level elevation change, enabling the assessment of strain localization mechanisms. We relocate 1716 earthquakes using a new 1‐D velocity model. Using a new local magnitude scaling with station corrections, we find 1 ≤ ML ≤ 4.5, and a b‐value of 1.22 ± 0.06. We present 59 first motion and 3 full moment tensor inversions, and invert for opening directions. We use complementary geodetic displacement vectors and strain rates to describe the geodetic strain field. Our seismic and geodetic strain zones demonstrate that only a small part of the 300 km‐wide region is currently active; low elevation and high‐elevation regions are active, as are areas with and without Holocene magmatism. Variations in the active plate boundary's location, orientation and strain rate appear to correspond to lithospheric heterogeneities. In the MER‐ER linkage zone, a belt of seismically fast mantle lithosphere generally lacking Recent magmatism is coincident with diffuse crustal deformation, whereas seismically slow mantle lithosphere and Recent magmatism are characterized by localized crustal strain; lithospheric heterogeneity drives strain localization. Plain Language Summary: Continental rifting involves the stretching, thinning, and heating of plates. Where present, magma adds heat, fluid, and new rock material into the plate, altering its physical and chemical properties. Pre‐existing lithospheric thickness variations and crustal shear zones may also influence when and where rifting occurs. Rifting processes can be monitored by tracking the vertical and horizontal movement of plates, and by analyzing earthquake patterns. To address debates concerning the role of plate thinning, magmatism, and pre‐rift lithospheric structures, we analyze new seismic and geodetic data from the Turkana Depression, a 300‐km‐wide region linking the Main Ethiopian Rift to the north and the Eastern Rift to the south. Additionally, the region has a failed Mesozoic rift with pre‐existing crustal shear zones. We identify regions that are actively deforming, defining the active plate boundary. The breadth of the actively rifting zone decreases above mantle low‐velocity zones, thinned mantle lithosphere, and/or hotter melt‐infiltrated zones. We also find little to no evidence of reactivation of faults within the thin crust of a failed Mesozoic rift that is circumnavigated by the active rifting in the region. Our findings suggest that differences in the plate‐scale physical and chemical properties dictate where and how faulting and magmatism occur. Key Points: New 1‐D velocity model relocates 1716 earthquakes with local magnitude ranging from 1 to 4.5 and b‐value of 1.22 ± 0.06 in Turkana DepressionBrittle strain localizes in narrow areas overlying uppermost mantle low velocity zones and avoids previously thinned crust of Mesozoic riftWe redefine the modern Nubia‐Somalia plate boundary across the Turkana Depression; only a part of the 300‐km‐wide region is active [ABSTRACT FROM AUTHOR]