The occurrence, distribution, ecological and health risk assessment of 5 antibiotics (CFM, ERY, LCM, SMD and SMX) in 32 drinking water reservoirs of a megacity (Shenzhen) in Guangdong–Hong Kong–Macao Greater Bay Area (GBA), were investigated. Among the above antibiotics, CFM was not detected, ERY, SMD, LCM and SMX were detected in 65.6%, 46.9%, 43.7% and 40.6% of samples, with concentrations of 1.594–7.605 ng·L−1, 0.335–6.695 ng·L−1, 0.288–7.878 ng·L−1 and 0.770–5.355 ng·L−1, respectively. The maximum concentration of ERY was detected in GT Reservoir, and those of the other 3 antibiotics were detected in SZ Reservoir. The ecological risk quotient (RQ) values for SMX in SZ, XL, YT, EJ, SY, TG, XK, GK, MK and GT reservoirs ranged from 0.1 to 1.0, indicating a median risk to aquatic organisms, the others posed insignificant risk or low risk. Considering the joint effects of detected antibiotics, the highest overall RQ value was 0.38, obtained in SZ Reservoir, in other words, it was exposed to greater risk. Based on health risk assessment, the health RQ values for the detected antibiotics were significantly lower than 0.01, indicating insignificant risk to human health. These findings could provide a scientific basis for the government to ensure the drinking water safety of a megacity in GBA.