Electrostatic discharge (ESD) events are the main factors impacting the reliability of Integrated circuits (ICs); therefore, the ESD immunity level of these ICs is an important index. This paper focuses on comprehensive drift-region engineering for ultra-high-voltage (UHV) circular n-channel lateral diffusion metal-oxide-semiconductor transistor (nLDMOS) devices used to investigate impacts on ESD ability. Under the condition of fixed layout area, there are four kinds of modulation in the drift region. First, by floating a polysilicon stripe above the drift region, the breakdown voltage and secondary breakdown current of this modulation can be increased. Second, adjusting the width of the field-oxide layer in the drift region when the width of the field-oxide layer is 5.8 μm will result in the minimum breakdown voltage (105 V) but the best secondary breakdown current (6.84 A). Third, by adjusting the discrete unit cell and its spacing, the corresponding improved trigger voltage, holding voltage, and secondary breakdown current can be obtained. According to the experimental results, the holding voltage of all devices under test (DUTs) is greater than that of the reference group, so the discrete HV N-Well (HVNW) layer can effectively improve its latch-up immunity. Finally, by embedding different P-Well lengths, the findings suggest that when the embedded P-Well length is 9 μm, it will have the highest ESD ability and latch-up immunity.