The Barcelona midfielder believes the match against England will show how far Spain have come.
Lopetegui was appointed in July following the retirement of Vicente del Bosque, who stood down after Spain followed up a group-stage exit at the 2014 World Cup with elimination in the last 16 at Euro 2016.
Lopetegui has won four and drawn one of his five games to date and Busquets believes the match against England, who are also rebuilding under Gareth Southgate, will show how far Spain have come.
"England are a great side full of top players," the 28-year-old Barcelona midfielder told Spain's pre-match press conference at Wembley.
"Like ourselves a little bit recently, they've not done so well in tournaments, whether it be the World Cup or the Euro.
"But it still makes it a big game tomorrow night, both for individuals within the Spanish set-up and as a team.
"We're a new group, with lots of new faces and youngsters who've joined the group recently and we've not played too many games with the manager.
"It's a great opportunity to fight against a top side and continue to progress as a team."
Busquets was handed his first Spain call-up for a friendly game against England in February 2009 and is due to win his 94th cap on Tuesday.
He was a member of the teams that triumphed at the 2010 World Cup and Euro 2012, but with a new side taking shape under Lopetegui, he says there is no need to dwell on past achievements.
"I'm one of the players who played a lot with Vicente. Obviously things went well, looking back, but I don't think it does any good in football to look backwards," Busquets said.
"You need to look forwards all the time. Obviously there were a lot of things that worked positively under the previous manager, but it's not about concentrating on what's changed or what hasn't changed.
"It's all about being united, being together as a group with the management and the coaching staff, and concentrating on the very, very important game tomorrow night that we're looking to win."
Like Southgate, Lopetegui is a former coach of the national under-21 team who was promoted to the senior role despite a relative lack of top-flight experience at club level.
Southgate, too, is undefeated, although he is yet to be officially confirmed as England's permanent manager, having taken over on an emergency basis following the departure of Sam Allardyce.
England are still to capture the imagination on Southgate's watch, having beaten Malta 2-0 and Scotland 3-0 and drawn 0-0 in Slovenia, but Lopetegui believes they are showing signs of progress.
"I think England are improving," said the former Porto coach.
"They show different skills in the offensive phase and I think they are trying to work on the offensive phase."
Asked about the similarities between himself and Southgate, Lopetegui replied: "You can see that. He has the challenge now. I think he's doing a very good job and I wish him the best."
Lopetegui will be without senior players Sergio Ramos, Gerard Pique, Jordi Alba, Andres Iniesta and Diego Costa due to injury against England.
Sergi Roberto, Cesar Azpilicueta, Isco, Nolito, Juan Mata and Jose Callejon could all start, while Manchester United midfielder Ander Herrera is in line to make a belated senior debut aged 27.
Manchester City playmaker David Silva trained apart from the rest of the squad on Monday, casting some doubt over his participation in the game.