Due to high altitudes, Central Asian alpine lakes can serve as indicators of localized climate change. This article monitored the water volume time series trends of the ungauged alpine Lake Karakul, which is typical because of the abundance of glaciers in the basin, from 1990 to 2020 via multiple source remote sensing data. The “Global-Local” multi-scale lake extraction method is used to delineate the boundary of Lake Karakul. Consistency analysis was performed on the altimetry data of CryoSat-2, ICESat-1 and ICESat-2, assuming that the lake surface was flat; a threshold value was set to remove gross error, and then 3σ was used to remove the surface elevation anomaly. Based on the pyramid volume model, the lake area and surface elevation information were used to reconstruct the water volume time series of Lake Karakul. The influencing factors of water volume temporal variation were discussed. The results show that Lake Karakul has been on an expansionary trend in recent years: The lake area increased from 394.9 km2 in 1988 to 411.4 km2 in 2020; the rate of increase is 0.74 m/year. The surface elevation increased from 3886.6 m in 2003 to 3888.6 m in 2020; the rate of increase is 0.11 km2/year. The lake water volume accumulated was 0.817 km3 in 2003–2020, with an accumulation rate of 0.059 km3/year. The Lake Karakul basin is developing towards dry heat, with a cumulative temperature variation rate of +0.38 °C/year; the average rate of variation in annual cumulative precipitation is −3.37 mm/year; the average evapotranspiration in the watershed is on a fluctuating increasing trend, with a rate of variation of +0.43 mm/year; glaciers in the lake basin have a retreating trend, with an average annual rate of variation of −0.22 km2/year from 1992 to 2020. Lake Karakul is more sensitive to temperature variations, and the runoff from retreating glaciers in the basin is an important contribution to the expansion of Lake Karakul.