Hojlund has scored 26 goals in 95 games for United, who he joined in a £72m move from Atalanta in August 2023.
He managed only four goals in the Premier League in 2024-25 but has now scored three times in five games for Napoli.
They have an obligation to buy the Denmark international for £38m at the end of the season if certain conditions are met, including Champions League qualification.
Hojlund showed pace and strength for his first goal when he collected De Bruyne’s through ball before clinically finishing past Sporting goalkeeper Rui Silva.
Matteo Politano fouled Maximiliano Araujo to concede a second-half penalty, which Suarez converted to make it 1-1, but Hojlund got the winner with a brave header following De Bruyne’s cross from the left touchline.
“Rasmus has a lot of quality and as a striker when you go forward you need that smell of goals – it’s really important for him and the team,” said De Bruyne.
“It’s a great night for him and it’s going to help us get more goals with him.”
De Bruyne, 34, won the Champions League with Manchester City in 2023.
He joined Napoli on a free transfer in June this year, and on Wednesday he ended a run of eight games in the competition without a goal or an assist.
The Belgian also became the sixth player to assist two goals in a Champions League game on five or more occasions, with the others being Angel di Maria (eight times), Ryan Giggs and David Beckham (both seven) and Lionel Messi and Zinedine Zidane (both five).
“Playing with an exceptional talent like Kevin de Bruyne is special,” said Hojlund. “I just need to get into space and he’ll get me the ball.”
Like Napoli, Sporting have now also won one and lost one of their two Champions League matches after they began with a 4-1 victory over Kazakh side Kairat.