This study analyzed monthly and inter-annual variability of mesoscale phenomena, including the El Niño Southern Oscillation (ENSO), the Pacific Decadal Oscillation (PDO) climate indexes and wind intensity considering their influence on sea surface temperature (SST) and chlorophyll a (Chl-a). These analyses were performed to determine the effects, if any, of climate indexes and oceanographic and environmental variability on the central and southern coastal ecosystem of Sonora in the Gulf of California (GC). Monthly satellite images of SST (°C) and Chl-a concentration were used with a 1-km resolution for oceanographic and environmental description, as well as monthly data of the climate indexes and wind intensity from 2002–2015. Significant differences (p > 0.05) were observed while analyzing the monthly variability results of mesoscale phenomena, SST and Chl-a, where the greatest percentage of anti-cyclonic gyres and filaments was correlated with a greater Chl-a concentration in the area of study, low temperatures and, thus, greater productivity. Moreover, the greatest percentage of intrusion was correlated with the increase in temperature and cyclonic gyres and a strong decrease of Chl-a concentration values, causing oligotrophic conditions in the ecosystem and a decrease in upwelling and filament occurrence. As for the analysis of the interannual variability of mesoscales phenomena, SST, Chl-a and winds, the variability between years was not significant (p > 0.05), so no correlation was observed between variabilities or phenomena. The results of the monthly analyses of climate indexes, environmental variables and wind intensity did not show significant differences for the ENSO and PDO indexes (p > 0.05). Nonetheless, an important correlation could be observed between the months of negative anomalies of the ENSO with high Chl-a concentration values and intense winds, as well as with low SST values. The months with positive ENSO anomalies were correlated with high SST values, low Chl-a concentration and moderate winds. Significant inter-annual differences were observed for climate indexes where the years with high SST values were related to the greatest positive anomaly of ENSO, of which 2002 and 2009 stood out, characterized as moderate Niño years, and 2015 as a strong El Niño year. The years with the negative ENSO anomaly were related to the years of lower SST values, of which 2007–2008 and 2010–2011 stood out, characterized as moderate Niñas. Thus, variability associated with mesoscale oceanographic phenomena and seasonal and inter-annual variations of climate indexes had a great influence on the environmental conditions of the coastal ecosystem of Sonora in the Gulf of California.