Wayne, clad in a crimson-red fitted hat and matching winter coat, arrived onstage at the New Orleans Arena to thunderous applause.
"I'm nothing without you," he told the crowd in response to his ovation, according to The Associated Press.
The rapper has been on a promotional tour with Young Money since earlier this month in support of the recently released We Are Young Money compilation.
The outing kicked off December 17 in Texas but hit a few speed bumps along the way. Earlier this month, the rapper and his entourage were detained by U.S. Border Patrol agents in the Lone Star State. Officials found marijuana on Lil Wayne's tour bus, but after being held for hours, he was later released and was never charged in the incident.
The New Orleans show went off without a hitch. During Young Money's performance of "Every Girl," the crowd cheered with approval. Stripped down to a tank top, Wayne was joined by Mack Maine, Jae Millz and Gudda Gudda for the number. Weezy pulled double-duty subbing for a missing Drake.
Wayne has a number of dates left on his tour, including appearances in Arizona and Mississippi. Next, Wayne and company are set to perform New Year's Eve at the San Diego Arena in California.