Background: Obesity is increasingly prevalent and has been associated with poorer outcomes and higher toxicity in breast cancer treatment. Its impact on tolerance to neoadjuvant chemotherapy (NAC) remains understudied. Objectives: This study aimed to determine the prevalence of overweight and obesity among patients with high-risk early-stage breast cancer (BC) treated with NAC. It evaluated the association between obesity and clinically significant chemotherapy-related toxicities. Pathological complete response (pCR), progression-free survival (PFS), and overall survival (OS) were explored. Methods: This is a retrospective cohort study on stage I–III BC assigned for NAC between January 2020 and December 2022. Patients were categorized by body mass index. Patients with obesity were compared with an age-matched non-obese cohort (1:1). The toxicities evaluated were hospitalization, dose reduction, treatment delay, or treatment discontinuation. Multivariable logistic regression models were performed, adjusting for age, comorbidity burden, and carboplatin use. Results: Of 487 eligible patients, 31.2% were overweight and 27.7% were obese. Peripheral neuropathy was more frequent and severe in obese patients (63.7% vs. 36.3%, p < 0.001). In multivariable analysis, obesity was independently associated with increased odds of global toxicity (OR = 1.83; 95% CI: 1.08–3.15; p = 0.027) and treatment discontinuation (OR = 2.30; 95% CI: 1.18–4.59; p = 0.016). Conclusions: Obesity is highly prevalent among high-risk early BC patients. It is independently associated with increased treatment-related toxicity, particularly discontinuation. These findings highlight the need for closer toxicity monitoring in patients with obesity. Reliance on BMI alone may be insufficient, underscoring the potential value of incorporating body composition assessment into clinical practice.