Surface waters from estuaries were reported to disseminate antibiotic resistance (AR), particularly from faecal coliforms of human origin introduced via domestic wastewater and surface runoffs. Thus, this study aimed to determine the concentration and antimicrobial susceptibility profiles of Escherichia coli isolated from surface waters of selected estuaries in the City of Manila. From a total of 48 water samples collected from six estuaries over a two-month period, the estimated average concentration of E. coli and total coliform are 4.3 × 104 CFU/100 mL and 11.0 × 104 CFU/100 mL, respectively. Among the isolates, 14.6% were identified as multidrug-resistant, while 6.3% were classified as extended-spectrum β-lactamase producers. Moreover, 18.8% of the isolates had a multiple antibiotic resistance index of ≥0.2. The findings indicate that AR E. coli contamination likely originates from human excretions, including those from informal settlements and hospital patients treated with multiple antibiotics. This makes these estuaries unsuitable for beneficial use due to the potential risk of exposure to MDR/ESBL E. coli and other faecal coliforms. Thus, urgent measures including law-enforced monitoring, management, rehabilitation, and education are necessary to curb faecal pollution and limit the spread of AR in these waters.