This study hypothesized that botulinum toxin (Botox) therapy would sustainably reduce sweat production in axillary hyperhidrosis patients over one year and significantly improve various quality-of-life aspects, including psychological well-being, social interactions, and daily functioning. The objectives were to quantitatively measure changes in sweat production and qualitatively assess the evolving impact on patients’ quality of life over one year. Conducted prospectively at the Pius Brinzeu Clinical Emergency Hospital in Timisoara, Romania, this study complied with ethical standards and included adults with primary axillary hyperhidrosis unresponsive to conventional treatments. Participants underwent Botox injections and were evaluated at baseline, six months, and one year, using the Hyperhidrosis Disease Severity Scale (HDSS), WHOQOL-BREF, and the Dermatology Life Quality Index (DLQI), among other tools. Involving 81 patients, the study showed significant improvements in sweat production and quality-of-life metrics. Sweat production decreased from 0.81 g to 0.23 g per 15 min over one year (p < 0.001). HDSS scores reduced from 3.4 to 1.5, indicating a decrease in symptom severity (p < 0.001). The DLQI total score, assessing life quality impact, notably dropped from 19.9 to 6.9 (p < 0.001). Quality-of-life domains also showed significant improvements, especially in the social (from 65.3 to 73.4, p < 0.001) and environmental aspects (from 68.0 to 72.1, p < 0.001). Higher HDSS and sweat production were significantly associated with a lower quality of life on the DLQI (B coefficients of −4.1 and −2.5, respectively). Botulinum toxin therapy proved effective in reducing sweat production and improving the quality of life in axillary hyperhidrosis patients over a one-year period. These improvements were statistically significant in both physical and psychosocial domains. The study highlights the potential long-term benefits of Botox therapy for hyperhidrosis.