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At present, fully mechanized cultivation (FMC) has begun to be utilized in commercial sugarcane production in China. To provide new insights into whether cane yield and health are altered by fully mechanized cultivations, the cane yield and endophytic microbial community structure in stems of sugarcane that underwent fully mechanized cultivation (FMC) and conventional artificial cultivation (CAC) were compared. The results showed that the diversity and richness of endophytic microorganisms, except for the bacterial richness in the stems of sugarcane, could be significantly increased by using FMC. Meanwhile, in comparison with CAC, the relative abundance of Proteobacteria and Ascomycota increased under FMC. Moreover, some dominant endophytic bacterial genera, such as <i>Acidovorax</i>, <i>Microbacterium</i>, and <i>Paenibacillus</i>, and some dominant endophytic fungal genera, such as <i>Scleroramularia</i>, <i>Tetraplosphaeria</i>, and <i>Dinemasporium</i>, were found to be significantly enriched in cane stems under FMC treatments. Additionally, the endophytic microbial functions in sugarcane stems were not significantly altered by FMC treatments. Our results suggest that cane growth, yield, and health are not significantly altered by FMC. The results also indicate that fully mechanized management can be developed as a sustainable method in sugarcane production.