Multiple myeloma (MM) is frequently associated with cytogenetic abnormalities, with high-risk cytogenetics linked to poorer survival. Acute kidney injury (AKI) is common in MM, but its relationship with high-risk cytogenetics remains underexplored. This study aimed to assess the association between high-risk cytogenetics and AKI in newly diagnosed MM patients and to evaluate their impact on overall survival, relapse-free survival, and progression to chronic kidney disease (CKD) in the first two years after diagnosis. We conducted a single-center retrospective cohort study including patients newly diagnosed with MM between 2018 and 2022. We enrolled 122 patients. AKI was observed in 36.9% of patients, rising to 62.3% among those with high-risk cytogenetics. High-risk cytogenetics (OR: 3.32; 95% CI: 1.17–6.40; p = 0.024), CKD (OR: 9.14; 95% CI: 2.92–18.65; p < 0.001), kappa free light chains, hypercalcemia, difference in free light chain (dFLC), and bone marrow plasmocyte percentage were independently associated with AKI. Both AKI (HR: 2.71; 95% CI: 1.18–6.23; p = 0.019) and high-risk cytogenetics (HR: 3.33; 95% CI: 1.13–9.76; p = 0.029) were independently associated with lower overall survival. Among survivors without prior CKD, progression to CKD was higher in those with AKI (30.7% vs. 9.3%; p = 0.041). High-risk cytogenetics were significantly associated with AKI in MM patients. Both factors independently predict worse survival and increased risk of CKD progression.