The present long-term (1993–2013) study was aimed at identifying the effects of global change on the environmental characteristics and the plankton community of the tropical, high-altitude Lake Alchichica, Puebla, Mexico. We found no statistically significant increasing trend in air temperature, but an increase from 2002 to 2013, and interannual variability in the meteorological variables. Accordingly, the water temperature rose from 1993 to 2003 and remained similar until 2013. Nonetheless, on a longer-term (1966-2018), longer than the period considered in the present study, air and water temperatures showed an increasing trend in the range considered indicative of climate change. The lake displayed a characteristic warm monomictic thermal pattern but exhibited interannual variability. The planktonic community composition and structure remained similar. The small chlorophytes (e.g., Monoraphidium minutum) dominated the phytoplankton abundance, while the large diatom Cyclotella alchichicana dominated the biomass. The calanoid copepod Leptodiaptomus garciai dominated both the zooplankton abundance and biomass. However, as the temperature increased the large-size phytoplankton (i.e., C. alchichicana) abundance and biomass increased, but the small-size phytoplankton abundance and biomass, as well as the adult copepod abundance and biomass, decreased. The increase in temperature could have favoured the large-size over the small-size phytoplankton. In addition, the temperature increase could have negatively affected the calanoid copepods in two different ways—direct association with the negative effects of higher temperatures on the physiology of the copepods, or indirect association with the negative effects of higher temperatures on the small-size phytoplankton, which diminish the copepods’ food resource.