Exposure to pathogens during wastewater treatment could result in significant health risks. In this paper, a probabilistic approach for assessing the risks of microbial infection for workers in an activated sludge wastewater treatment plant is presented. A number of exposure routes were modelled, including hand-to-mouth and droplet ingestion of untreated wastewater, droplet ingestion and inhalation of aerosols after secondary treatment, and ingestion of sludge during drying. Almost all workers exposed to untreated wastewater could be infected with the three selected potential pathogens of pathogenic E. coli, Norovirus and Cryptosporidium spp. Hand-to-mouth ingestion is the single most significant route of exposure at the head of works. There is also a risk of infections resulting from ingestion of droplets or inhalation of aerosols at the aeration tanks or contaminated hands at the clarifiers during secondary wastewater treatment. For sludge, the risks of infection with Norovirus was found to be the highest due to accidental ingestion (median risks of 2.2 × 10−2(±3.3 × 10−3)). Regardless of the point and route of exposure, Norovirus and Cryptosporidium spp. presented the highest risks. The study finds that occupational exposure to wastewater at wastewater treatment plants can result in significant viral and protozoan infections. This risk assessment framework can be used to establish and measure the success of risk reduction measures in wastewater treatment plants. These measures could include the use of personal protective equipment and adherence to strict personal hygiene.