The long-term human activities could influence land use/cover change and sustainability. As the global climate changes, humans are using more land resources to develop economy and create material wealth, which causes a tremendous influence on the structure of natural resources, ecology, and environment. Interference from human activities has facilitated land utilization and land coverage change, resulting in changes in land-use intensity. Land-use intensity can indicate the degree of the interference of human activities on lands, and is an important indicator of the sustainability of land use. Taking the middle and lower reaches of Shule River Basin as study region, this paper used “land-use degree (LUD)” and “human activity intensity (HAI)” models for land-use intensity, and analyzed the spatio-temporal variation of land-use intensity in this region from a multi-perspective. The results were as follows: (1) From 1987 to 2015, the land use structure in the study region changed little. Natural land was always the main land type, followed by semi-natural land and then artificial land. (2) The LUD in the study region increased by 35.36 over the 29 years. It increased the most rapidly from 1996 to 2007, and after 2007, it still increased, but more slowly. A spatial distribution pattern of “low land-use degree in east and west regions and high land-use degree in middle region” changed to “high land-use degree in east and middle regions and low land-use degree in west region”. (3) The human activity intensity of artificial lands (HAI-AL) in the study region decreased from 1987 to 1996, and then increased from 1996 to 2015. The human activity intensity of semi-artificial lands (HAL-SAL) in the study region increased over the 29 years, and more rapidly after 1996. (4) 1996–2007 was a transition period for the land-use intensity in the study region. This was related to the implementation of the socio-economy, policies such as “Integrated Development of Agricultural Irrigation and Immigrant Settlement in Shule River Basin (1996–2006)”, and technologies.