We analyzed the effect of conditional, αMHC-dependent genetic β-catenin depletion and stabilization on cardiac remodeling following experimental infarct. β-Catenin depletion significantly improved 4-week survival and left ventricular (LV) function (fractional shortening: CT^Δex3–6: 24 ± 1.9%; β-cat^Δex3–6: 30.2 ± 1.6%, P < 0.001). β-Catenin stabilization had opposite effects. No significant changes in adult cardiomyocyte survival or hypertrophy were observed in either transgenic line. Associated with the functional improvement, LV scar cellularity was altered: β-catenin-depleted mice showed a marked subendocardial and subepicardial layer of small cTnT^pos cardiomyocytes associated with increased expression of cardiac lineage markers Tbx5 and GATA4. Using a Cre-dependent lacZ reporter gene, we identified a noncardiomyocyte cell population affected by αMHC-driven gene recombination localized to these tissue compartments at baseline. These cells were found to be cardiac progenitor cells since they coexpressed markers of proliferation (Ki67) and the cardiomyocyte lineage (αMHC, GATA4, Tbx5) but not cardiac Troponin T (cTnT). The cell population overlaps in part with both the previously described c-kit^pos and stem cell antigen-1 (Sca-1)^pos precursor cell population but not with the Islet-1^pos precursor cell pool. An in vitro coculture assay of highly enriched (>95%) Sca-1^pos cardiac precursor cells from β-catenin-depleted mice compared to cells isolated from control littermate demonstrated increased differentiation toward α-actin^pos and cTnT^pos cardiomyocytes after 10 days (CT^Δex3–6: 38.0 ± 1.0% α-actin^pos; β-cat^Δex3–6: 49.9 ± 2.4% α-actin^pos, P < 0.001). We conclude that β-catenin depletion attenuates postinfarct LV remodeling in part through increased differentiation of GATA4^pos/Sca-1^pos resident cardiac progenitor cells.