This article explores the relationship between vertical wind shear (VWS) and tropical cyclone (TC) genesis in the Mozambique Channel (MC) for the period 1979–2019. Additionally, SST, low-level relative vorticity, 700 hPa relative humidity and upper-level divergence were also analyzed for the peak cyclogenesis months to explore their relative contributions. The analyses were done using NCEP/NCAR Reanalysis-1 for the atmospheric fields, monthly Optimum Interpolation SST V2, and for the cyclogenesis the TC best track data from the La Reunion–Regional Specialized Meteorological and Joint Typhoon Warning Centre. A total of 43 TCs generated in the MC were observed for the analysed period. The maximum frequency of cyclogenesis in the MC was observed during January and February and the spatial location of maximum TC genesis was coincident with the minimum values of the VWS. The VWS showed significant correlations with TC intensity, particularly when considering the upper atmosphere (200–500 hPa) or the bulk (200–850 hPa) VWS. The mean composites of the cyclogenesis months over the MC of SST, relative humidity at 700 hPa, divergence at upper atmosphere, showed significant values. However, linear correlations between these factors vs. TC genesis frequency and intensity were not significant. Analyses of interannual correlations between VWS and Niño-3.4 (subtropical southwest Indian Ocean dipole-SIOD) showed statistically significant positive (negative) correlations at different lags, suggesting that La Niña and the positive phase of SIOD conditions are favorable to weaker VWS and thus to intensification of TCs in the Mozambique Channel. Thirteen landfall cases were observed with seven over the Madagascar west coast and six over the Mozambique coast. The landfall over the Madagascar (Mozambique) coast was associated with strengthened (weakened) VWS.