Understanding the spatial growth of cities is crucial for proactive planning and sustainable urbanization. The largest and most densely inhabited megapolis of Pakistan, Karachi, has experienced massive spatial growth not only in the core areas of the city, but also in the city’s suburbs and outskirts over the past decades. In this study, the land use/land cover (LULC) in Karachi was classified using Landsat data and the random forest algorithm from the Google Earth Engine cloud platform for the years 1990, 2000, 2010, and 2020. Land use/land cover classification maps as well as an urban sprawl matrix technique were used to analyze the geographical patterns and trends of urban sprawl. Six urban classes, namely, the primary urban core, secondary urban core, sub-urban fringe, scatter settlement, urban open space, and non-urban area, were determined for the exploration of urban landscape changes. Future scenarios of LULC for 2030 were predicted using a CA–Markov model. The study found that the built-up area had expanded in a considerably unpredictable manner, primarily at the expense of agricultural land. The increase in mangroves and grassland and shrub land proved the effectiveness of afforestation programs in improving vegetation coverage in the study area. The investigation of urban landscape alteration revealed that the primary urban core expanded from the core districts, namely, the Central, South, and East districts, and a new urban secondary core emerged in Malir in 2020. The CA–Markov model showed that the total urban built-up area could potentially increase from 584.78 km2 in 2020 to 652.59 km2 in 2030. The integrated method combining remote sensing, GIS, and an urban sprawl matrix has proven invaluable for the investigation of urban sprawl in a rapidly growing city.