Maguire, wearing the captain's armband, headed his side in front after 18 minutes and Sancho's fine finish put the hosts in cruise control before half-time.
It was quite a turnaround for Maguire who was sent off in England's last game, a 1-0 Nations League defeat by Denmark.
England's performance was also a welcome distraction after a difficult week in which Liverpool defender Joe Gomez suffered a serious knee injury in training with the national team and FA chairman Greg Clarke resigned after making inappropriate comments at a parliamentary committee meeting.
Remarkably, England's last six completed matches against Ireland had ended in draws with the game in Dublin in 1995 abandoned because of crowd trouble.
But the latest meeting proved far less eventful and completely one-sided as Southgate's young team impressed.
"We used the ball very well, created a lot of chances. We could have been more comfortable if we had taken some of those chances but overall very pleased," Southgate said.
An added bonus was a debut for 17-year-old Borussia Dortmund midfielder Jude Bellingham who came on in the second half to become the third youngest player to represent England, behind Theo Walcott and Wayne Rooney.
Ireland, who were drafted in to replace New Zealand as England's opponents, enjoyed a decent opening 10 minutes but after that were outclassed.
Coady has been forced to self-isolate having discovered he had inadvertently come into contact with somebody prior to camp who has tested positive for COVID-19 via an NHS Test and Trace alert.
The Wolverhampton Wanderers defender had returned two negative tests as part of The FA and UEFA's protocol but, in line with UK Government guidelines, has to adhere to a period of self-isolation.
Meanwhile, Rashford's arrival into camp had initially been delayed to allow for further assessment on an injury sustained last weekend but the Manchester United forward will now not meet up.