Aguirre took charge of Japan in July following the resignation of Alberto Zaccheroni, which was prompted by a dismal World Cup campaign that saw the Asian nation claim just one point from three group-stage games.
And the former Mexico boss has been quick to make his mark, axing an array of World Cup flops in a much-changed first squad.
Only 12 players from the World Cup made it into Aguirre's 23-man squad for the Uruguay game, with record cap-holder Yasuhito Endo among those to be omitted.
A total of five debutants have been included by Aguirre, and the remodelled hosts will likely need to be at their best if they are to claim victory over a talented Uruguay team that will have been disappointed not to make it beyond the last 16 in Brazil.
Uruguay, though, will not be able to count on the presence of coach Oscar Tabarez, who will miss this encounter and next Tuesday's friendly with South Korea after undergoing back surgery last month.
Under-20 coach Fabian Coito is to step into the breach in Tabarez's stead, although he will not be able to call on star striker Luis Suarez.
Suarez was left out of Uruguay's squad, despite being permitted to compete in friendly matches for club and country following an appeal against his four-month ban from football-related activity for biting Italy's Giorgio Chiellini during a World Cup group clash.
The absence of Suarez – who will be unable to play in next year's Copa America – has afforded uncapped attackers Jonathan Rodriguez and Diego Rolan the opportunity to make their international bow.
Midfielders Giorgian De Arrascaeta and Camilo Mayada and defender Mathias Corujo have also been called up for the first time as Uruguay begin their preparations to retain the Copa America title they won three years ago in Argentina.
Despite the absence of Suarez, Japan defender Maya Yoshida anticipates a difficult contest at the Sapporo Dome but is focused on moving on from a miserable World Cup campaign ahead of the 2015 AFC Asian Cup.
"As you know, Uruguay is one of the top teams in the world, even without Suarez," Yoshida told Japan's Kyodo News agency.
"But it is up to us to show our quality to the new coach and the supporters as well because the supporters were disappointed about the results at the World Cup.
"The World Cup was not a great experience for us.
"As the gaffer (Aguirre) said, we should focus on getting the title again at the Asian Cup in the winter. Now a new chapter starts for us."
