Large scale additive manufacturing (AM) of fiber-reinforced polymer composites has gained traction in the mold and die community over the last decade, largely due to reduced material cost and lead time. However, limitations in mold size remain present due to printer volume constraints and costs associated with large format machines. This paper describes a method for producing additively manufactured polymer molds in segments with an O-ring joint design, which can be machined and subsequently assembled for autoclave applications. The developed joining mechanism allows for maintaining the vacuum integrity during the cure cycle while accounting for the anisotropic nature of the additively manufactured polymer molds. Over a range of tested temperatures, 20–200 °C, the multi-part mold joining design was able to achieve full vacuum of ∼73.7 cmHg (29 inchHg) and maintain a vacuum integrity with vacuum losses less than 1.5 cmHg/5min (0.6 inchHg).