The 23-year-old joined Antonio Conte’s side on loan last summer following the arrival of new star striker Benjamin Sesko at Old Trafford.
Hojlund has had some good moments back in Italy, scoring 14 goals and providing five assists in his 42 games.
Following their 3-0 Serie A win over Pisa, Napoli’s £38 million option to buy became an obligation as they secured a top four finish.
Taking to Instagram, Hojlund sent an ‘emotional’ message to Man United fans, saying: "To say goodbye to Manchester United is something that kinda feels emotional too.
“My childhood dream came true by playing at Old Trafford in a red jersey," he wrote.
"The way you fans supported me, made me feel like home and let me find my confidence again is something I’m so grateful for.
“So the goal today symbolizes a new confident start, in which I will give everything for the time ahead to Napoli, and a thank you to all the fans, players and staff of Manchester United who made the dream I had as a kid come true.
“It’s time for new dreams, so let’s chase them."