The African nation took a first-minute lead, but Grealish quickly levelled.
Skipper James Ward-Prowse's penalty put England ahead, before Nathan Redmond's screamer and another from Grealish gave them a 4-1 half-time lead.
Cauley Woodrow's shot was deflected in by a Guinea defender, with the Fulham forward adding two more in an easy win.
Gareth Southgate's men opened the tournament with a 1-0 win over Portugal on Thursday, Chelsea midfielder Lewis Baker scoring the winner.
Next they meet Paraguay on Wednesday, rounding off their group campaign against Japan on Friday.
"We spoke before the game about any team being capable of scoring against you," Southgate said. "We started in a sloppy manner, so that was disappointing.
"Our response was good, we showed composure to work our way back into the game. The goal difference might end up being important.
"But if we start games like that against better opposition, it will be a struggle to get back into it."
England: Gunn, Stephens, Holding, Hause (Chambers 54), Targett, Ward-Prowse (Chalobah 41), Swift, Grimes, Grealish (Watmore 60), Redmond (Palmer 54), Woodrow. Subs not used: Pickford, Iorfa, Loftus-Cheek, Baker, Chilwell.
Jack Grealish scored twice on his full debut as England Under-21s continued their perfect start to the Toulon Tournament by thrashing Guinea.