A total of 46 crude oil samples recovered from the surrounding Niuzhuang sag were investigated to gain insight into the petroleum systems in the Dongying depression. Chemometrics identified four genetically distinct oil families. Family 1 fails to match any of the source rocks that have been discovered thus far. The candidate source rock must contain algal organic matter that could produce more negative carbon isotopic composition, large quantities of wax, C29 steranes, and tricyclic terpenoids compared to the Eocene Shahejie (Es) Formation intervals Es3 and Es4 and deposited in a reducing, stratified saline water environment. Family 2 is featured by high ratios of sterane/hopane, gammacerane/hopane, and C35/C34 homohopane and low pristane/phytane ratios. The source rock is the upper Es4 interval. Family 3 is characterized by distinctive or even opposite features to family 2. The source rock is the lower Es3 interval. Family 4 is a mixed oil derived from the lower Es3 and upper Es4 source rocks at different thermal maturation. Three end-member oil samples, EM1, EM2, and EM3, were identified by alternating least-squares. As a minor contributor, EM1 has an average value of 10%. As the main contributors, EM2 and EM3 average 53% and 37%, respectively. Oil samples from EM1 and EM2 are derived from the upper Es4 source rock, but EM1 was generated at a lower thermal maturity than EM2. Oil from EM3 was derived from the lower Es3 source rock at peak hydrocarbon generation.