This study aims to reveal the runoff variation characteristics of long time series in a karst region, analyse comprehensively its different driving factors, and estimate quantitatively the contribution rates of climate change and human activities to net runoff variation. Liudong river basin, a typical karst watershed in southwest China, is the study site. Statistical methods, such as linear fitting, the Morlet wavelet analysis, normalized curve and double mass curve, are applied to analyse the runoff of the watershed. Results show that the runoff in the karst watershed during the research period exhibits a three-stage change and the abrupt change points are the years 1981 and 2007: (1) 1968 +/- 1980, the runoff initially exhibited a trend of sustained decreasing and then an abrupt fluctuation. The runoff was obviously destroyed through precipitation-producing processes. Improper land utilisation and serious forest and grass destruction intensified the fluctuation variation amplitude of the runoff. (2) 1981 +/- 2006, the changing processes of runoff and precipitation exhibited good synchronism. Precipitation significantly affected runoff variation and human activities had a slight interference degree. (3) 2007 +/- 2013, the fluctuation range of runoff was considerably smaller than that of precipitation. The significant growth of forest and grassland areas and the increase in water consumption mitigated runoff fluctuation and greatly diminished runoff variation amplitude. According to calculation, the relative contribution rates of precipitation and human activities to net runoff variation with 1981 +/- 2007 as the reference period were -81% and 181% in average, respectively, during 1968 +/- 1980, and -117% and 217% in average, respectively, during 2007 +/- 2013. In general, the analysis of runoff variation trend and of the contribution rate of its main influencing factors in the typical karst watershed for nearly half a century may be significant to solve the drought problem in the karst region and for the sustainable development of the drainage basin.