Chimeric antigen receptor (CAR) T cell therapy has transformed cancer treatment but is limited by poor persistence and exhaustion, contributing to relapse. IKZF1 (Ikaros), a transcription factor involved in asymmetric cell division (ACD), has been implicated in promoting memory-like T cell differentiation. Here, we evaluated the effect of a gain-of-function (GOF) IKZF1 variant on CAR T cell phenotypes using lentiviral transduction and CRISPR-Cas9-mediated homology-directed repair (HDR) knock-in. Lentiviral transduction achieved strong CAR and mCherry expression but modest Ikaros protein increases. CRISPR knock-in at the native IKZF1 locus achieved ~81% editing efficiency while preserving CAR expression and T cell viability. GOF-IKZF1 knock-in CAR T cells displayed elevated CD62L and CD25 expression, consistent with a central memory-like phenotype. Persistence and exhaustion assays showed sustained CCR7⁺ CD45RA⁻ phenotypes over 29 days and significantly reduced PD-1 expression, with CD39 and KLRG1 also trending downward. These findings demonstrate that GOF-IKZF1 reinforces memory differentiation and delays exhaustion, enhancing CAR T cell durability. This work not only provides a mechanistic framework for understanding IKZF1’s role in T cell fate but also identifies a promising engineering strategy to overcome persistence-related relapse, advancing the development of next-generation CAR T therapies with improved long-term efficacy.