It has been widely accepted since the 1980s that Seram crude oils belong to one family that originated from the Triassic carbonate source rock. Even though these oils share similar nature and origin, they exhibit wide physio-chemical composition variations in Seram Basin. Moreover, this variation is also noted within a similar oil field. Hydrocarbon alteration, especially biodegradation, a process of hydrocarbon destruction by microbial activities, has been attributed to this variation. However, the degree and extension of biodegradation in the Seram Basin are still poorly understood. Therefore, crude oils accumulated in main reservoirs, the Pre-Tertiary Manusela Carbonate and the Pliocene Fufa Clastic reservoirs, retrieved from Lofin, Oseil, Nief, and Bula Fields, are comprehensively studied. In addition, several oil seep samples were also utilized for this study together with crude oil geochemistry data compiled from previous publications. The occurrence of biodegradation is also validated with the geological conditions that include resevoir temperatures and salinities. Based on the geochemical signatures, there is a wide range of biodegradation degrees within the Seram Basin with the biodegradation degree tends to increase and more destructive to Bula Field which is situated in the northern part of the basin. The biodegradation pattern is linked to hydrocarbon generation and migration history. The Neogene deformation in eastern Indonesia is interpreted to be responsible for the different biodegradation process within Seram Basin. This process should be well understood and not be neglected during petroleum exploration, especially in eastern Indonesia. This study shows that such simple process has a deep meaning on the petroleum system history, especially the hydrocarbon preservation in the reservoir.