City brushed aside Bundesliga runners-up RB Leipzig 6-3 in an entertaining encounter in Manchester.
Grealish got on the scoresheet with a 56th minute strike to make it 4-2, as Christian Nkunku netted a hat-trick for the Germans.
Continental success has eluded City despite their increased spending over the past decade but they have come close in recent seasons.
City were beaten 1-0 in last season’s Champions League final by Chelsea, having made the semi-finals in 2020-21.
“The players are always talking about (last season’s final),” said Grealish, who joined City from Aston Villa in August.
“They’re determined to go one better this year. It’s a good start for us. Hopefully we can go all the way this time.”
Grealish cut on off the left flank before curling in a right-foot strike after dribbling into the box for his goal.
“It’s great to get the win and obviously a great night for me personally,” he said. “To get the goal, it’s a wonderful feeling.”
He added: “It was a good one. I think Rben (Dias) got a touch and I managed to cut inside the defender.
“I was happy with the finish and I’m obviously really pleased.”
The result gives City an early lead in Group A with Paris Saint-Germain having been held to a 1-1 draw at Club Brugge.