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The impact of global warming across northwestern Mexico is difficult to discern because long-term climatic data series are lacking, and this semi-arid region is subject to strong seasonal variability. Using data between 1922 and 2004 from 55 weather stations located in the State of Sonora, the Baja California Peninsula, and some stations in the United States near the Mexican border, we analyzed trends observed for weather variables. The magnitude and statistical significance of trends were determined, using the least squares regression procedure. Microregional series were delimited after applying varimax rotated empirical orthogonal functional analysis to the weather series. The limits between the 9 microregions were defined by considering a rotated factor loading >= 0.6. Series with significant trends were correlated with 5 different climatic indices: Pacific Decadal Oscillation, Atlantic Multi-decadal Oscillation, Southern Oscillation Index, North Atlantic Oscillation Index, and values of 700 hPa geopotential height anomalies. Results show that northwestern Mexico has high meteorological heterogeneity, as observed in spatial and seasonal variability of precipitation and temperature. Different trends were found across the region. Correlation analyses indicate that trends in several variables are associated with inter-decadal changes in the Pacific and the Atlantic, as well as with variations of the 700 hPa atmospheric flow patterns, changes in sea surface temperatures, penetration of extratropical fronts, and, for the State of Baja California Sur, higher incidence of tropical cyclones.