In the face of scarce public health resources, it is critical to understand which disease surveillance strategies are effective, yet such validation has historically been difficult. From May 1 to December 31, 2021, a cohort study was carried out in Santa Clara County, California, in which 10,131 high-quality genomic sequences from COVID-19 polymerase chain reaction tests were merged with disease surveillance data. We measured the informational value, the fraction of sequenced links surfaced that are biologically plausible according to genomic sequence data, of different disease surveillance strategies. Contact tracing appeared more effective than spatiotemporal methods at uncovering nonresidential spread settings, school reporting appeared more fruitful than workplace reporting, and passively retrieved links through survey information presented some promise. Given the rapidly dwindling cost of sequencing, the informational value metric may enable near real-time, readily available evaluation of strategies by public health authorities to fight viral diseases beyond COVID-19.