The replacement of native vegetation by pastures or tree plantations is increasing worldwide. Contradictory effects of these land use transitions on the direction of changes in soil organic carbon (SOC) stocks, quality, and vertical distribution have been reported, which could be explained by the characteristics of the new or prior vegetation, time since vegetation replacement, and environmental conditions. We used a series of paired-field experiments and a literature synthesis to evaluate how these factors affect SOC contents in transitions between tree- and grass-dominated (grazed) ecosystems in South America. Both our field and literature approaches showed that SOC changes (0–20 cm of depth) were independent of the initial native vegetation (forest, grassland, or savanna) but strongly dependent on the characteristics of the new vegetation (tree plantations or pastures), its age, and precipitation. Pasture establishment increased SOC contents across all our precipitation gradient and C gains were greater as pastures aged. In contrast, tree plantations increased SOC stocks in arid sites but decreased them in humid ones. However, SOC losses in humid sites were counterbalanced by the effect of plantation age, as plantations increased their SOC stocks as plantations aged. A multiple regression model including age and precipitation explained more than 50% (p < 0.01) of SOC changes observed after sowing pastures or planting trees. The only clear shift observed in the vertical distribution of SOC occurred when pastures replaced native forests, with SOC gains in the surface soil but losses at greater depths. The changes in SOC stocks occurred mainly in the silt+clay soil size fraction (MAOM), while SOC stocks in labile (POM) fraction remained relatively constant. Our results can be considered in designing strategies to increase SOC storage and soil fertility and highlight the importance of precipitation, soil depth, and age in determining SOC changes across a range of environments and land-use transitions.