Irrigation is an agronomic practice of major importance in alfalfa (Medicago sativa L), especially in the semiarid environments of Southern Europe. Field experimentation was conducted in Western Greece (2016–2018) to evaluate the effects of irrigation timing on weed presence, alfalfa yield performance, and forage quality. In a randomized complete block design (four replications), two cultivars (“Ypati 84” and “Hyliki”) were the main plots, while three irrigation timings were the subplots (split-plot). The irrigation timings were IT-1, IT-2, and IT-3, denoting irrigation 1 week before harvest, 1 week after harvest, and 2 weeks after harvest, respectively. IT-1 reduced Solanum nigrum L. density by 54% and 79% as compared to IT-3 and IT-2, respectively. Chenopodium album L. density was the highest under IT-2. IT-3 resulted in 41% lower Amaranthus retroflexus L. density in comparison to IT-2, while the lowest values were observed under IT-1. Stand density and stems·plant−1 varied between years (p ≤ 0.05). Mass·stem−1 and alfalfa forage yield were affected by the irrigation timings (p ≤ 0.001). Total weed density and forage yield were negatively correlated in both the second (R2 = 87.013%) and the fourth (R2 = 82.691%) harvests. IT-1 and IT-3 increased forage yield, leaf per stem ratio, and crude protein as compared to IT-2. Further research is required to utilize the use of cultural practices for weed management in perennial forages under different soil and climatic conditions.