Significance Although immune checkpoint blockade therapies have achieved long-term responses in several malignancies, in colorectal cancer (CRC) patients clinical benefit is observed only in heavily mutated tumors that are mismatch-repair–deficient or have high microsatellite instability. This limitation urges the identification of novel immune escape mechanisms and the design of additional immunotherapeutic modalities. We show that Galectin-1 (Gal-1) confers immune privilege to CRC by increasing the frequency of CD8 ⁺ CD122 ⁺ PD-1 ⁺ regulatory T cells (Tregs) and accentuating their immunosuppressive activity in experimental models. Accordingly, analysis of CRC patient datasets revealed a “poor prognosis signature” characterized by high Gal-1 expression and elevated CD8 ⁺ Treg score. Thus, targeting Gal-1/glycan interactions may represent a potential immunotherapeutic modality for treating CRC by recalibrating the CD8 ⁺ Treg compartment.