Carbon isotope analyses of fluid inclusion gases trapped in quartz grains in nine sandstone core samples from eight wells in the Baiyun depression and the Panyu lower uplift were performed to determine the source and thermal maturity of the paleo-natural gases. Two-dimensional thermal and hydrocarbon generation history modeling of the source rocks coupled with the carbon isotopic results of the fluid inclusion gases were used to understand the natural gas accumulation process and locate the active gas source rocks in the Baiyun depression. The fluid inclusion gases were generated from oil-prone Wenchang Formation source rocks of high thermal maturity (1.7%–3.1% vitrinite reflectance [Ro]), with most Ro values between 2.1% and 2.7% Ro. The mixing of Wenchang Formation–sourced gas of high thermal maturity with Enping Formation–sourced oil-associated gas of relatively low thermal maturity resulted in relatively lighter carbon isotopes of the reservoired gases compared to the fluid inclusion gases. Gas mixing could have occurred during the main Enping Formation–sourced oil charge period based on the hydrocarbon generation history modeling results. This study confirms the presence of oil-prone semideep-water and deep-water lacustrine facies source rocks in the Wenchang Formation of the Baiyun depression, which are widely developed with great thicknesses based on the seismic facies interpretations. However, successful oil and gas exploration in the deep-water area should consider the distribution of active gas source rocks in the Wenchang Formation because the depth of the base of the active source rock greatly decreases from shallow-water to deep-water areas, which increases exploration risk in deep-water and ultradeep-water areas.