The southwestern slope of Lufeng Depression, which is located in the central part of Zhu I Depression is a significant geomorphic unit due to its petroliferous discoveries and tectonic evolutions since early Palaeogene. Based on the comprehensive analysis of cores, wireline logs, seismic volumes, and other related geological and geophysical information, the sequence architecture and depositional evolution was analysed, and their responses to regional tectonic processes and base‐level changes were revealed. The results indicated that two second‐order sequences and six third‐order sequences defined by different types of sequence boundaries are recognized. The second‐order and third‐order sequences were bounded by regional erosional unconformities on the depression margin or slope and unconformities in the central depression with the assist of stacking patterns of wireline logs and depositional characteristics of cores. The second‐order sequence generally consists of two regional transgressive–regressive cycles which can be further subdivided into several local sub‐cycles equivalent to corresponding third‐order sequences which can be identified from wireline logs and cores. The palaeogeomorphology resulted from compound and complex tectonic events in the early Palaeogene plays an important and main role in controlling sequence architecture. In contrast, the base‐level changes largely controls the sequence architecture in the late Palaeogene. The depositional systems within the sequence stratigraphic framework are mainly composed of braided delta deposits and shore deposits, which respectively includes braided channel, subaqueous distributary channel, lacustrine shale, beach bar, maximum flooding surface, shoreface, and foreshore. The base‐level changes, which apparently originated from tectonic uplift and subsidence and sediment supply, controlled the regional transgressions and regressions in sedimentary facies distributions. The development of subsequence (what we call it sand units or sections) from 2,980 to 2,880 in Enping Formation in the Early Palaeogene is obviously influenced by a decrease in tectonic subsidence (rifting stage) and an increase in accommodation space (base‐level rising), while the case is opposite in subsequence 2,850 of Enping Formation. However, the subsequence in Zhuhai Formation in the late Palaeogene from 2,760 to 2,600 was formed in stable tectonic settings (transition stage), and thereby, it was mainly dominated by base‐level changes which were caused by sediment supply and accommodation space changes.