Djokovic couldn't defend his Australian Open title last month because he was deported from the country for being unvaccinated.
The United Arab Emirates allowed him entry, and Djokovic cashed in at a tournament he's won five times. The Monday crowd was glad to see him, as he was met with a standing ovation, complete with phone cameras flashing when he was introduced. Djokovic responded with an emphatic wave before making his way to his position by the judge's chair.
Musetti took two sets off Djokovic at the French Open last year, but on a breezy Dubai evening, the Italian wild card couldn't convert bags of break chances while trailing 3-1 in the first set and 4-2 in the second.
"I have to be satisfied with my tennis, especially after not playing for two and a half, three months," Djokovic said on court. "Of course, there were moments when I played great, there were moments when I made a couple of unforced errors in a row uncharacteristically. But it's normal to expect that [in my] first match after a while."
He next faces Karen Khachanov or Alex de Minaur.
The Associated Press contributed to this report.