This study aimed at testing the effectiveness of novel combinations of chemical and physical methods to control Prosopis juliflora, an invasive weed in the Moshi and Simanjiro districts of Nothern Tan-zania. Six different treatments including manual uprooting, glyphosate, bark chop with chemical application, two separate chemical mixtures and control were tested in a total of 32 plots, which represented two land use types (grazing land and farmland) found in the two districts. Each plot covered 20m×30m plot area. Two response variables (stem count and tree volume) were recorded to compare weed population density before and after treatment six months later. An analysis of the untreated control plots, showed that the inherent growth potential of P. juliflora was higher in Moshi than in Simanjiro district. The number of stems increased during the experiment for all six treatments showing that the P. juliflora population had not yet reached the local carrying capacity. For the manual control treatment, the increase was reduced compared to the untreated control. For all other treatments, the increase in stem count was on par with that in the untreated control or even higher. Thus, we conclude that only manual uprooting had a controlling effect but not to the extent that it eradicated P. juliflora. Thus, it is for P. juliflora as for weed control in general: weed control must be an ongoing effort.