Congenital cytomegalovirus (cCMV) infection is a leading cause of sensorineural hearing loss (SNHL) and neurodevelopmental disabilities in children worldwide. Some regions in the United States and Canada have implemented universal newborn screening for cCMV, which requires molecular diagnostic technologies for identifying cCMV, such as PCR testing of newborn dried blood spots (DBS). This study aimed to evaluate the sensitivity of droplet digital PCR (ddPCR) compared to quantitative real-time PCR to detect CMV DNA in newborn DBS. The limit of detection of various ddPCR primer/probe combinations (singleplex UL55-HEX, singleplex UL83-FAM, and multiplex UL55-HEX/UL83-FAM) was evaluated using the National Institute of Standards and Technology’s (NIST) CMV quantitative standard. Singleplex UL55-HEX ddPCR exhibited the lowest limit of detection among the primer/probe combinations tested for ddPCR. UL55 ddPCR was then compared to real-time PCR in 49 infants with confirmed cCMV identified through newborn screening for CMV in saliva swabs and confirmed by a urine test. The results showed that ddPCR was only positive for 59% (29 out of 49) of the cCMV infants, while real-time PCR was positive for 80% (39 out of 49). Due to its lower sensitivity and throughput, ddPCR may not be suitable for cCMV newborn screening.