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This study investigates the mechanisms of generation of the transient transmission common-mode noise in a differential serpentine delay line under weak coupling condition. The generation mechanism and the frequency of common-mode noise are investigated with reference to the time-domain transmission waveform and the differential-to-common mode conversion mixed-mode S-parameters using the circuit solver HSPICE and 3-D full-wave simulator HFSS, respectively. The generation mechanisms of common-mode noise include length mismatch between vertical-turn-coupled traces, the length effect of parallel-coupled traces, and the crosstalk noise effect. Moreover, a graphical method based on wave tracing is presented to illustrate the cancellation mechanism of near-end common-mode noise for the symmetrical differential serpentine delay line. Some practical, commonly used layout routings of the differential serpentine delay line are investigated. Some important design guidelines are provided to help design differential serpentine delay line with low common-mode noise. A comparison between simulated and measured results validates the equivalent circuit model and analytical approach.