Super Bowl XLIX took place on February 1, 2015, in Glendale, Arizona. In preparation for this event and associated activities, the Maricopa County Department of Public Health (MCDPH) developed methods for enhanced surveillance, situational awareness, and early detection of public health emergencies. Surveillance strategies implemented from January 22 to February 6, 2015, included enhanced surveillance alerts; animal disease surveillance; review of NFL clinic visits; syndromic surveillance for emergency room visits, urgent care facilities, and hotels; real-time onsite syndromic surveillance; all-hazards mortality surveillance; emergency medical services surveillance, review of poison control center reports; media surveillance; and aberration detection algorithms for notifiable diseases. Surveillance results included increased influenzalike illness activity reported from urgent care centers and a few influenza cases reported in the NFL clinic. A cyanide single event exposure was investigated and determined not to be a public health threat. Real-time field syndromic surveillance documented minor injuries at all events and sporadic cases of gastrointestinal and neurological (mostly headaches) disease. Animal surveillance reports included a cat suspected of carrying plague and tularemia and an investigation of highly pathogenic avian influenza in a backyard chicken flock. Laboratory results in both instances were negative. Aberration detection and syndromic surveillance detected an increase in measles reports associated with a Disneyland exposure, and syndromic surveillance was used successfully during this investigation. Coordinated enhanced epidemiologic surveillance during Super Bowl XLIX increased the response capacity and preparedness of MCDPH to make informed decisions and take public health actions in a timely manner during these mass gathering events.