Cross-laminated timber (CLT) is an increasingly popular wood-based alternative for large building applications. CLT panels are typically not treated due in part to a perceived lack of efficient and effective methods for treating large panels and a lack of information on what effect treatment processes may have on the panels' mechanical properties. We propose that treating CLT panels with borate solution, applied under vacuum in flexible bags, could provide a practical and effective option for providing preservative protection for interior applications. Samples were cut from commercially produced CLT panels and treated with borate solution using vacuum. The samples were then evaluated for preservative retention, swelling, and degradation of mechanical properties. Initial treatments resulted in a wide range of preservative retentions and property effects among the products tested. In subsequent adjustments, the treatment parameters were changed to provide consistent and sufficient retention among the products. The vacuum treatment method effectively penetrated cracks in the lumber and the bond lines (adhesive joint between adjacent lamellae). Swelling and effects on mechanical properties were minimal in the adjusted samples. In addition to these samples that were treated in a rigid pressure vessel, a larger sample was successfully treated in a flexible plastic bag. Data from this study support the concept that vacuum treatment of CLT panels with borate can provide sufficient levels of preservative retention, can be adjusted to the material being treated, and has minimal effects on mechanical properties.