Introduction: Uterine fibroids, also known as leiomyomas, are benign smooth muscle tumors of the uterus that affect up to 75% of women during reproductive years. Their growth is influenced by estrogen, genetic mutations such as MED12, and local growth factors. Clinically, they present with abnormal uterine bleeding, pelvic pressure, infertility, and adverse pregnancy outcomes. The Ki-67 antigen, a nuclear protein expressed during active phases of the cell cycle, is widely used as a proliferation marker. Its role in assessing tumor activity and severity in leiomyomas remains important for diagnostic and prognostic purposes. Aim and Objective: The study aimed to evaluate Ki-67 expression in uterine leiomyomas and adjacent healthy myometrium and to assess its potential as a marker for tumor activity and severity across different morphological subtypes. Methodology: This cross-sectional study was conducted at Santosh Medical College and Hospital, Ghaziabad, on 86 female patients aged 35–44 years with uterine leiomyomas scheduled for hysterectomy. Patients with prior hormonal therapy, other uterine pathologies, or previous uterine surgery were excluded. Tissue samples of leiomyoma and adjacent myometrium were collected and subjected to immunohistochemical staining for Ki-67. Expression was evaluated by two blinded observers, and statistical analysis was performed using Student’s t-test and ANOVA with p < 0.05 considered significant. Results: The majority of participants were in the 38–40 years age group (37.2%). Most had secondary education (38.4%) and belonged to the upper lower socioeconomic class (33.7%). Mean Ki-67 expression was significantly higher in leiomyomas (4.32 ± 1.67) than in myometrium (1.14 ± 0.61; p < 0.001). Among subtypes, atypical leiomyomas showed the highest expression (6.12 ± 2.05), followed by cellular (5.41 ± 1.83), ordinary (3.85 ± 1.42), and degenerated (2.67 ± 0.98). All subtypes had significantly higher expression than corresponding myometrium (p < 0.001). Conclusion: Ki-67 expression was significantly elevated in leiomyomas compared to myometrium, with higher levels in atypical and cellular subtypes, suggesting its potential utility as a marker for tumor activity and severity in uterine leiomyomas.