The former Spain youth coach has taken over at the Estadio do Dragao after Paulo Fonseca left the club in March.
Luis Castro had taken interim charge before Lopetegui's appointment was confirmed on Monday and the incoming coach takes up the position following spells with Rayo Vallecano and Real Madrid B.
A former goalkeeper for the likes of Rayo, Barcelona and Real Madrid, Lopetegui is looking forward to implementing his philosophy at the Portuguese club.
"It is a pleasure and an honour. I will be part of the history of this great club and I admit I wish I could keep up with half the energy the chairman has been showing," he said.
"We have a game plan we want to implement, a philosophy, but we need to understand the context and the players we will find.
"Above all, we want to assure the effort and the commitment of everyone, especially the players, so we can shine in all competitions and all matches we play.
"We will have energy, ambition, strength. We will work hard to bring joy to the fans and to be a winning team again."
Lopetegui won both the Under-19 and U21 European Championships with Spain, but faces a challenge to return the Primeira Liga title to Porto due to Benfica's current dominance.
Jorge Jesus' side wrapped up the league last month, but Porto chairman Jorge Nuno Pinto da Costa believes Lopetegui's experience in Spain can stand the club in good stead.
"It is my pleasure to present our new coach, who I believe doesn’t need to be introduced after his victorious career in Spain and on whom we fully trust," he said.
"That is why we offered him a three-year contract, as we want to build a solid team, who will guarantee we will go back to what we have been.
"It wasn't by chance that Spain won European titles at Under-19 and Under-20 (level) two years in a row and they have the best league in the world, in my opinion.
"That was why Lopetegui was my choice. When I contacted him, I told him he was my first, second and third choice, and gave him no chances to say no."
