Theileria annulata, a transforming apicomplexan parasite, subverts host chromatin architecture to drive leukocyte transformation and immune evasion. To uncover the ubiquitin-linked epigenetic mechanisms underpinning this process, we profiled the chromatin landscape of infected bovine lymphocytes using integrated proteomic, imaging, and functional assays. Notably, T. annulata lacks the DNA damage marker γH2A.X and its SQ/TQ motif, suggesting evolutionary divergence from canonical ubiquitin-mediated DNA repair signaling. High-resolution mapping of histone post-translational modifications revealed nuclear compartmentalization, with host-enriched marks (H3K27me3, H3K9me1/2) and parasite-predominant modifications (H3K4me3, H3K18me1, H3K27ac, H3K9ac, H3K36me3). A pronounced reduction in H3K9me3 levels indicated chromatin destabilization, which persisted even after parasite clearance. Pharmacological reactivation of TP53 triggered apoptosis, revealing a reciprocal feedback loop between TP53 and SUV39H1: TP53 activation suppressed SUV39H1 and H3K9me3, while SUV39H1 inhibition restored TP53 function. This ubiquitin-sensitive TP53–SUV39H1 axis emerges as a central epigenetic circuit exploited by the parasite to suppress apoptosis and sustain a cancer-like phenotype. Our findings position T. annulata as a model of ubiquitin-linked epigenetic parasitism and highlight chromatin vulnerabilities as actionable targets in parasite-induced oncogenic transformation.