Tesho Akindele scored the fastest goal in club history as Orlando got off to a quick start at home to Jaap Stam's Cincinnati on Sunday (AEST).
Akindele found the back of the net after just 33 seconds, surpassing the Orlando record set by Chris Mueller (62 seconds) in April 2018.
Nani doubled the lead in stunning fashion in the 19th minute, the former Manchester United star leaving Yuya Kubo on the floor after cutting to his right foot and then his left as he curled the ball past Przemyslaw Tyton.
After Nani hit the post minutes later and saw his shot saved by Cincinnati goalkeeper Tyton just past the hour mark, Junior Urso sealed the victory with 10 minutes remaining.
Orlando, which remains unbeaten through three games, is third in the Eastern Conference, behind leader New England Revolution and second-placed New York City.
Revolution edged Atlanta United 2-1 and New York City defeated reigning Supporters' Shield winner Philadelphia Union 2-0.
Earthquakes and Dallas, meanwhile, both won 4-1 against DC United and Portland Timbers respectively.
Jackson Yueill's brace and a pair of assists from Cade Cowell fuelled the Earthquakes, who are top of the Western Conference on goal difference but level on points with Real Salt Lake, LA Galaxy and Austin FC.
Dallas showed no mercy at home to the Timbers after Andres Ricaurte and Jader Obrian scored in the opening 13 minutes.
Real Salt Lake came from behind to top Sporting Kansas City 3-1 courtesy of Rubio Rubin's second-half double, while MLS newcomer Austin prevailed 1-0 against Minnesota United.
Elsewhere, New York Red Bulls was a 2-0 winner over Chicago Fire, defending champion Columbus Crew was held to a goalless draw by Montreal Impact and Houston Dynamo and Los Angeles FC played out a 1-1 draw.