To limit introduction of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), the United States restricted travel from China on February 2, 2020, and from Europe on March 13. To determine whether local transmission of SARS-CoV-2 could be detected, the New York City (NYC) Department of Health and Mental Hygiene (DOHMH) conducted deidentified sentinel surveillance at six NYC hospital emergency departments (EDs) during March 1–20. On March 8, while testing availability for SARS-CoV-2 was still limited, DOHMH announced sustained community transmission of SARS-CoV-2 (1). At this time, twenty-six NYC residents had confirmed COVID-19, and ED visits for influenza-like illness increased, despite decreased influenza virus circulation.The following week, on March 15, when only seven of the 56 (13%) patients with known exposure histories had exposure outside of NYC, the level of community SARS-CoV-2 transmission status was elevated from sustained community transmission to widespread community transmission (2). Through sentinel surveillance during March 1–20, DOHMH collected 544 specimens from patients with influenza-like symptoms (ILS)§ who had negative test results for influenza and, in some instances, other respiratory pathogens.All 544 specimens were tested for SARS-CoV-2 at CDC; 36 (6.6%) tested positive. Using genetic sequencing, CDC determined that the sequences of most SARS-CoV-2–positive specimens resembled those circulating in Europe, suggesting probable introductions of SARS-CoV-2 from Europe, from other U.S. locations, and local introductions from within New York. These findings demonstrate that partnering with health care facilities and developing the systems needed for rapid implementation of sentinel surveillance, coupled with capacity for genetic sequencing before an outbreak, can help inform timely containment and mitigation strategies. The DOHMH collected deidentified remnant nasopharyngeal swab specimens from patients with ILS and no known virologic diagnosis evaluated at six sentinel EDs during March 1–20, 2020. Because of concern that SARS-CoV-2 could be introduced by travelers returning from China, where the outbreak originated, five EDs were selected because of their high use by patients residing in ZIP codes with ≥20% self-identified Chinese speakers. Two EDs were in Manhattan, two in Queens, one in Brooklyn, and one in the Bronx. Refrigerated specimens were released to DOHMH 48 hours after collection, and frozen specimens were released 1 week after collection. Specimens collected during March 1–9 were from patients of all ages. Because little was known about pediatric SARS-CoV-2 infection, during March 10–20, DOHMH only collected specimens from patients aged <18 years. Specimens were sent to CDC on March 23, 2020, for SARS-CoV-2 testing using the 2019-nCoV real-time reverse-transcription–polymerase chain reaction (RT-PCR) assay.. To conserve resources, pools with up to five specimens were tested together, and individual specimens within positive or inconclusive pools were retested. Nucleic acid from RT-PCR–positive specimens was then extracted and subjected to Oxford Nanopore MinION sequencing, and full genome sequences were generated using methods described previously (3). Phylogenetic relations were inferred using the Nextstrain pipeline (4), including the 36 positive SARS-CoV-2 sentinel specimens and selected full genome sequences available as of April 1, 2020, from the Global Initiative on Sharing All Influenza Data (GISAID) (5). This project was determined by DOHMH and CDC to be nonresearch public health surveillance. Therefore, approval by the agencies’ institutional review boards was not required. Given limited testing availability, and to better understand prevalence of SARS-CoV-2 infections in the absence of NYC population prevalence data, DOHMH calculated the estimated weekly number of persons with undetected SARS-CoV-2 infection in the target population. DOHMH estimated the weekly target population, defined as those persons evaluated at any NYC ED with ILS who had negative test results for influenza (and, in some instances, for other respiratory pathogens). Numbers of ED visits for ILS were obtained using ED syndromic surveillance data and aggregated weekly citywide and by sentinel ED. Each sentinel ED provided DOHMH their weekly influenza testing volume and results. Estimated SARS-CoV-2 prevalence among the target population was calculated using the estimated true prevalence too assuming 85% test sensitivity (range = 75%–95%) and 99% specificity of the SARS-CoV-2 RT-PCR assay; results were analyzed using R statistical software (version 3.6.3; The R Foundation). During March 1–20, 544 specimens were collected from the six sentinel EDs (Table). Thirty-six (6.6%) specimens were positive for SARS-CoV-2, including 22 (5.2%) among 425 patients of all ages and 14 (11.8%) among 119 patients aged <18 years. Among the 36 SARS-CoV-2–positive specimens, 32 (89%) were obtained during two 3-day periods: March 8–10 and March 17–19 (Figure). The estimated SARS-CoV-2 prevalence among patients of all ages in the target population was 0.3% during the week of March 1 and 11.3% during the week of March 8, with an estimated 15 and 1,170 undetected SARS-CoV-2 infections among patients of all ages in the target population during each respective week (Table). The estimated SARS-CoV-2 prevalence among patients aged <18 years in the target population was 2.0% during the week of March 8 and 17.7% during the week of March 15, with an estimated 103 and 227 undetected SARS-CoV-2 infections among patients aged <18 years in the target population during each respective week (Table). During the weeks of March 1 and March 8, there were 26 and 1,917 confirmed cases of COVID-19, respectively, in NYC among persons of all ages. During the weeks of March 8 and March 15, there were 42 and 457 confirmed cases of COVID-19, respectively, in NYC among persons aged <18 years (Table). Full genome sequences were generated from all 36 positive SARS-CoV-2 specimens. All sequences fell across three arbitrarily defined groups (A, B, and C) (Supplementary Figure, Two of the NYC sequences clustered in Group A, which contains sequences primarily derived from cases diagnosed in patients in the United States, who were mostly from the state of Washington, and includes other sequences from New York. Seven sequences clustered in Group B, which includes early sequences detected in China and other global sequences, as well as other sequences from New York. The remaining 27 sequences most closely clustered with New York sequences within Group C, which was largely dominated by sequences detected in Europe and North America.