The singer-turned-actor wowed the crowd in New Orleans, Louisiana when he ended his longtime hiatus and returned to the stage in a black tuxedo, opening his concert on the eve of the American football championships with his 2002 debut solo track Like I Love You.
Timberlake, backed by a 10-piece band, played for 90 minutes and pulled out all the stops by bringing out Jay-Z to perform their new single Suit & Tie off his upcoming album, The 20/20 Experience, and Timbaland for their classic hit SexyBack.
His set list also included crowd favourites Senorita, Cry Me a River and Summer Love, as well as a cover of INXS' What You Need and a perfectly-choreographed rendition of The Jacksons' Shake Your Body (Down to the Ground).
Timberlake, who married Jessica Biel in October, also used the opportunity to debut two new songs, titled Little Pusher Love Girl and That Girl.
Sir Paul McCartney, John Legend and Sofia Vergara were in the crowd for Timberlake's comeback gig, which came just eight days before he performs at the Grammy Awards on 10 February.