Metritis is major postpartum disease in dairy cows causing reduced milk production, impaired fertility, and substantial economic losses. Although treatment with β-lactam antibiotics is the main therapeutic option for treating cows with metritis, ~35% of cows fail to respond to treatment. Herein, we used whole-genome shotgun sequencing (WGS) to shed light of uterine microbiome, antimicrobial resistance genes (ARGs), and virulence factors genes (VFGs) profiles of cows that cured or failed to cure of metritis after treatment with ceftiofur or ampicillin. Uterine swabs were collected for each cow at the time of metritis diagnosis (D1) and 5 d later (D6) one day after treatments finished. Half of the cows (12/24) cured after the 5-d treatment (7 from ampicillin and 5 from ceftiofur). Our WGS revealed that over time (from d1 to d6) the mean relative abundance (MRA) of the genera Bacteroides, Prevotella, Alistipes, Fusobacterium, and Tannerella were reduced (P < 0.01), whereas Porphyromonas was increased (P < 0.01) independent of treatment (P > 0.05). For cows responding to treatment for metritis, only Streptococcus MRA was increased when compared with counterparts that did not cure of metritis. Beta-diversity decreased (P < 0.01) after treatment independent of treatment type (P > 0.05) and cure status (P > 0.05). Antibiotic treatment independent of type decreased VFGs abundance (P < 0.01), but increased ARGs (P < 0.01) abundance. Tetracycline resistance genes dominated the resistome of metritic cows, but β-lactam ARGs such as CMY-2 were not changed by treatment (P > 0.05) or time (P > 0.05). The ARGs TetT and TetW increased over time (P < 0.01) independent of treatment (P > 0.05) or cure status (P > 0.05). A higher MRA and presence of virulence factors for Streptococcus spp., Mycoplasma pneumoniae, and Vibrio cholerae were identified suggesting these bacteria and VFGs may be linked to metritis pathogenesis. In conclusion, antimicrobial treatment over time (from D1 to D6) independent of type and ability to cure metritis altered uterine microbiome, reduced VFG abundance and increased ARGs abundance.