Merritt captured his first US Indoors title since 2012, the year he also won the world indoor and Olympic hurdles titles, in 7.51 seconds edging Aleec Harris by .03 of a second.
"I'm just happy to come out here and get the win," Merritt said. "It proves I've still got it and I'm going to give it all I've got."
The 31-year-old from Chicago, who holds the 110m hurdles world record of 12.80, said he was in some ways "relieved" after missing last year's Rio Olympics because his trail leg was in pain the entire 2016 season.
The three-day meet at high altitude in Albuquerque, New Mexico, concluded with wins by a host of US Olympic standouts plus some impressive newcomers.
Ronnie Baker, coming off World Indoor Tour wins at Torun and Birmingham, matched the sixth-best time ever clocked to win the 60 meters in 6.45 seconds.
"I had the notion I could do something pretty special," Baker said. "We've been practising for this ever since October.
"My biggest goal right now is to make the world championship team this summer and make the Olympic team in 2020."
Also taking a first US Indoor 60m crown was Rio 4x400 US gold medal relay member Morolake Akinosun, who ran 7.08 to edge Dezerea Bryant by .03 for the women's win.
