Although public health surveillance data suggest an overall low prevalence of reported neurosyphilis cases (<2%), neurosyphilis and ocular syphilis clusters have recently been observed in multiple urban areas. The STD Surveillance Network (SSuN) Enhanced Neuro/Ocular Syphilis Surveillance project was established in 2016 to help address gaps in surveillance of early syphilis (ES) cases with neurologic and/or ocular manifestations. This study aimed to: (a) characterize prevalence of self-reported symptoms among reported ES cases in select participating jurisdictions (Florida Department of Health; Multnomah County Health Department; New York City Department of Health and Mental Hygiene; Philadelphia Department of Public Health; and Washington State Department of Health); and (b) describe clinical management of identified cases. 13,071 ES cases were reported across participating jurisdictions between November 1, 2016 and October 31, 2017. 9,123 (70%) were interviewed and received enhanced screening involving a standardized neurosyphilis and ocular syphilis data collection tool to supplement routine health department activities and case investigation protocols. Of interviewed cases, > 80% identified as male and men who have sex with men, and almost half were living with HIV. 151 (1.7%) reported at least 1 neurologic or ocular symptom: headache was most common, followed by blurry vision, vision changes, and tinnitus; stroke-like symptoms were least common. 35% of symptomatic cases underwent lumbar puncture (LP), with subsequent documentation of abnormal CSF results in 42%. Among cases with abnormal CSF, 95% received a CDC-recommended regimen for neurosyphilis or ocular syphilis treatment. Of symptomatic cases with no documented LP, 12% were ultimately treated for and/or clinically diagnosed with neurosyphilis or ocular syphilis. Of cases reporting at least 1 ocular symptom, one-third had documented ophthalmologic examination (of which less than half had abnormal findings such as uveitis, optic neuritis, or retinitis). Of cases reporting only ocular symptoms, 37% underwent LP, of which 53% had abnormal CSF results.