Urbanization is an important aspect of land use and cover change, which profoundly affects ecosystem composition, structure and function as well as regional landscape pattern and processes. The rapid development of small- and medium-sized cities is a significant characteristic of global urbanization today, and is expected to remain so for decades in the future. During the last 50 years, the fastest growing cities in China are small- and medium- sized cities with populations ≤ 500 thousands. Thus, small- and medium-sized cities are important for regional social development and urbanization, which has significant impacts on the sustainability of the regions and the entire nation. In the past 20 years, because of the rapidly rising number of small- and medium-sized cities, their urbanization effects have received increasing attention. Understanding the generalities and idiosyncrasies of the urbanization patterns and processes of these cities is crucial for sustainable development. However, much of the current research on urbanization has focused primarily on the large cities with populations > 500 thousands. Few studies have investigated the complexity and dynamics of small- and medium-sized cities, including the relationship between urban landscape patterns and urban ecosystem functions. In this study, we selected 24 small- and medium- sized cities in Xinjiang and the Yangtze River Delta region to quantify landscape change and underlying driving forces in the two regions using a comparative approach. Based on the results of our study, we concluded: (1) In the two regions, urban land type had the highest growth rate with a mean annual increase of > 5%, suggesting a rapid urbanization process from 1986 to 2000. However, the specific changes of land use and land cover types differed in the two regions. In the Yangtze River Delta, cropland declined in area significantly more than other types, with a mean annual decrease rate of 62.87 km². In the Xinjiang region, the areas of unused land and grassland declined substantially during the study period. The mean annual decrease rates of these two land-use types were 123.6 km² and 90.2 km², respectively. (2) The overall pattern of landscape change in the two regions was similar during the 15 years. The level of landscape fragmentation, landscape diversity, and patch shape complexity all increased. However, the urban landscape pattern among different cities in the Yangtze River Delta region became more homogeneous compared to the Xinjiang region. (3) Our comparison of the main forces driving landscape change in the two regions indicated that the changes in croplands contributed significantly to the changes in the overall landscape pattern of small- and medium- sized cities. In the Yangtze River Delta, the main driving forces of landscape change were associated with population growth and rural-to-urban migration of people. A large quantity of cropland was used for urban construction and became increasingly fragmented as urbanization unfolded. In contrast, the main driver of landscape change in the Xinjiang region was related predominantly to the increase in croplands due to population growth and immigration. In this case, the increased human activity resulted in the increase in cropland. Urban sprawl contributed relatively less to landscape pattern change in Xinjiang than in the Yangtze River Delta. In addition, the expansion of croplands not only took up a large amount of grassland resources, but also intensified land use on the grasslands, consequently leading to degradation of the grassland ecosystems. These findings provide useful information for dealing with ecological and environmental problems induced by rapid urbanization, and for sustainable development of small- and medium-sized cities in China. Further studies are needed to investigate the processes and mechanisms of how urbanization affects biodiversity and ecosystem services in these small- to medium-sized cities.