This study investigated improvements in sugarcane ethanol production by adapting yeast strains for very high gravity fermentation. Two yeast strains (C22 and Y904) were adapted in eight fermentation cycles with increasing initial sugar content from 56.2 to 296.1 g L⁻¹ (Experiment 1). After the last cycle, the “adapted” yeasts were recycled in a wort containing 296.1 g L⁻¹ initial sugar and compared with their respective strains that were not subjected to the adaptation process (Experiment 2). Fermentative parameters were analyzed and the osmotic stress on yeast cell morphology was assessed by scanning electron microscopy (SEM). In Experiment 1, along the fermentation cycles, strain Y904 showed a decrease in cell viability after sugar concentration of 223 g L⁻¹. SEM images showed that Y904 cells were wrinkled after this cycle. In the case of strain C22, no differences in cell viability were observed along the cycles. However, for both strains, the residual sugars were relatively high and the ethanol content was below the maximum potential. In Experiment 2, for strain Y904, no differences were observed between adapted and non-adapted yeasts in terms of ethanol content, cell viability, and morphology. In the case of strain C22, cell viability and final ethanol content were significantly higher in the adapted yeast, which had cells less damaged by the osmotic stress. In conclusion, the study supports the importance of yeast strain selection and adaptation for efficient VHG fermentation, by demonstrating the superior performance of yeast strain C22 in response to increasing initial sugar content.