Lake ice phenology is a sensitive indicator reflecting global warming. In this article, the long-term changes in lake ice phenology of the second-largest lake at Tibetan Plateau (i.e., the Nam Co) in response to climate change are investigated based on mathematical modeling. The model has been testified capable of reproducing daily surface temperature of the lake in both frozen and unfrozen seasons. The lake ice phenology determined according to the simulated lake surface temperature is found consistent with that derived from satellite observations. For the Nam Co during the period 1978–2017, the freezing date has been delayed (reached up to 0.57 days/year), whereas the thawing date became earlier (−0.23 days/year). The trend of lake ice phenology is significantly correlated to the annual minimal lake surface and air temperature. Modeling experiment suggests that lake ice phenology of the Nam Co is very sensitive to a warmer climate. Under warmer future, much later freezing date and earlier thawing date are expected; hence the ice-covering duration would be significantly shortened.