Research is needed to look for plants or lines that can thrive on soils affected by water deficit or other constraints. The present work investigated the potentiality of Saccharum spontaneum L. spp. aegyptiacum (Willd.) Hack., a lignocellulosic, perennial, rhizomatous, no-food crop in semi-arid Mediterranean area. A 3-year field trial was carried out with the aim to evaluate its physiology, biomass yield, water use efficiency, and biomass quality under different soil water availability. During 2011/2012, 2012/2013, and 2013/2014 growing seasons (hereinafter referred as 2011, 2012, and 2013, respectively), three levels of maximum evapotranspiration restitution (ETm) were compared: I 100 (100% ETm restitution), I 50 (50% ETm restitution), and I 0 (rainfed condition). Net photosynthesis, stomatal conductance, and transpiration rate were strictly related to the available soil water content (ASWC), with maximum gas exchange at field capacity. However, gas exchange between plants and atmosphere was also measured when ASWC was close to wilting point. Biomass dry matter (DM) yield and main morpho-biometric traits (e.g., stem height and basal stem diameter) were significantly affected by ASWC. A non-linear model showed that maximum DM yield, 37.86 Mg ha −1 , can be achieved when 1150 mm of water were used by the crop. Water use efficiency (WUE) was always highest in rainfed condition ( I 0 ), however, only in 2013 I 0 was significantly higher than I 50 and I 100 (5.89 g L −1 vs 4.26 and 3.33 g L −1 ). Within the variables employed, a linear model showed that WUE was negatively related to crop water use (CWU). The fiber content was not affected by the irrigation treatments. In the average, hemicellulose, cellulose, and lignin accounted for 23.9 (% w/w), 35.0 (% w/w), and 19.9 (% w/w), respectively. On the other hand, moisture and ash content, bulk density, low heating value, and ash melting point resulted significantly affected by the treatment. Present results suggested that S. spontaneum spp. aegyptiacum possesses a range of agronomically desirable traits of biomass crop: C4 plant, high biomass yield, active assimilation rates during drought–stress periods, able to use water efficiently, and satisfactory biomass quality.