Shiga toxin-producing Escherichia coli (STEC) pose a significant risk of outbreaks and can lead to serious complications, such as hemolytic uremic syndrome (HUS), in children and the elderly. STEC outbreaks documented in France are primarily associated with the consumption of raw milk cheeses and raw or undercooked ground beef. Surveillance of STEC infections in France relies in part on monitoring HUS in children under 15 years of age. On February 10, 2022, Santé publique France and the National E. coli Reference Center identified an excess of pediatric HUS cases reported since early February. The affected children were older than those usually affected and resided primarily in the northern half of France. Epidemiological investigations were initiated on February 11, 2022, by Santé publique France in collaboration with regional units to identify a possible common source of contamination in order to guide appropriate management measures. A confirmed case was defined as a person who, as of January 1, 2022, presented with an STEC infection caused by one of the epidemic strains of STEC O26:H11 or O103:H2 identified through whole-genome sequencing (WGS). A probable case was defined as a person who, since January 1, 2022, has presented with HUS and has an epidemiological link to a confirmed case, but without isolation of an STEC strain. Epidemiological investigations were conducted using an exploratory questionnaire to identify the food and environmental exposures of the patients. Data from loyalty cards of the stores frequented by the patients’ families were collected to identify food purchases and guide traceability investigations. The STEC strains isolated from patients were characterized and compared using multi-locus variable-number tandem repeat analysis (MLVA) and whole-genome sequencing (WGS). A case-control study was conducted to test hypotheses regarding an association between the illness and suspected food sources; controls were recruited from household members of GrippeNet/COVIDNet.fr participants. Fifty-seven confirmed cases (55 infected with an STEC O26:H11 strain, two infected with an STEC O103:H2 strain) and two probable cases were identified. The dates of symptom onset ranged from January 18 to April 5, 2022. The median age was six years (range: <1–40 years). Among the 58 pediatric cases, 50 (86%) developed HUS, two of whom died. Initial investigations identified several suspect foods consumed by a majority of cases, including ground beef patties and foods from a single fast-food chain, but traceability investigations ruled out these leads. Analysis of loyalty card data identified frequent purchases of frozen pizzas from brand A (B-range), and a second questionnaire administered to families confirmed frequent consumption of these pizzas by the affected individuals. The case-control study supported this hypothesis, given a highly significant association between the illness and the consumption of brand A frozen pizza (Odds Ratio: 116 [95% CI: 27–502]). Traceability investigations identified that brand A-range B pizzas were manufactured in France on a single production line. This line of pizzas was produced using a leavened dough that was not pre-baked before sale. Samples of Brand A, Line B pizza dough collected from the home of a confirmed case and from the manufacturer’s sample library tested positive for the epidemic strains of STEC O26:H11 and O103:H2. A sample of flour used by Company A to manufacture the implicated pizzas also tested positive for the epidemic strain of STEC O26:H11. On March 18, Company A initiated a nationwide recall of all pizzas in the B range. In total, 41 of the 55 cases (75%) who reported consuming pizzas cited brand A-B line. Among the 46 cases for which proof of pizza purchase was documented, 44 (96%) purchased brand A-B line. In the scientific literature, the risk of STEC infection linked to the consumption of undercooked flour is well known, and several flour-based foods have been implicated in various outbreaks, particularly in the United States and Canada. However, frozen pizzas are an unusual vehicle for STEC contamination because the expected cooking times and temperatures should be sufficient to eliminate these bacteria. This vehicle, combined with the consumption by patients of several foods at risk of STEC contamination, made the investigations particularly complex. The use of loyalty card data proved essential in directing the investigations toward A-gamme B brand pizzas. Following this outbreak, which appears to once again illustrate the risk of STEC infection linked to flour and flour-based products, a risk analysis is expected to better understand the diversity of contamination sources and document the persistence of STEC in foods intended to be cooked by consumers, such as raw pizza dough. These findings are essential for both food industry operators and food safety authorities to ensure risk management and adapt recommendations for consumers.