Lopetegui was sacked by Spain on the eve of last year's World Cup for agreeing to take charge of Real Madrid, where he then lasted only four and half months, following a disappointing start to the season.
After losing arguably the two biggest jobs in Spanish football inside half a year, Lopetegui has been given the chance to rebuild his reputation at Sevilla.
"I take this job with the utmost enthusiasm and ambition to try to do the absolute best I can do," Lopetegui said at a press conference a day after his appointment on Tuesday.
"I am eager to achieve the goals the club has and in that regard, we are ambitious. Nobody will beat us for ambition and motivation.
"We know we will have to work hard, that we cannot just talk a good game, and if we do, I are sure we will succeed."
Lopetegui's appointment is the first big decision of Sevilla's sporting director Monchi, who had been linked with Arsenal before deciding to return in March to the club where he previously spent 17 years.
Monchi would not confirm the club's specific aims under Lopetegui but the minimum requirement is likely to be Champions League qualification.
Sevilla missed out last season after finishing sixth in La Liga, with Pablo Machin sacked in March and his stand-in Joaquin Caparros failing to earn the job long-term.
"Julen is the coach that we identified that gave us the most confidence that we can meet our objectives," Monchi said.
"My first and only option was Julen and once we decided on him there has never been any doubt."
Neither Spain nor Real Madrid benefitted from their snap decisions to remove Lopetegui. Spain were beaten by Russia in the last 16 of the World Cup while Madrid finished the season 19 points behind Barcelona, after also sacking his replacement Santiago Solari.
Madrid had taken only 14 points from a possible 30 under Lopetegui, with a 5-1 defeat to Barca at Camp Nou proving the final straw.
Monchi is confident Lopetegui will bounce back. "I will be in the background," Monchi said. "But the only thing I am sure of is that this bet will pay off."