ORLANDO, Fla.—The deadliest shooting attack in U.S. history killed at least 49 people at a popular gay nightclub here, injured 53, left a community and nation in grief and reignited concern about homegrown American terrorists.

Authorities said Omar S. Mateen opened fire at the Pulse nightclub in downtown Orlando in an onslaught that sent patrons scrambling for the exits. Many remained trapped inside in what became an hourslong siege. During the attack, Mateen took time to call 911 and claim allegiance to Islamic State, officials...