The 21-year-old midfielder, who has operated primarily from left-back this season, saw off competition from City team-mate Rayan Cherki, Manchester United's Kobbie Mainoo, Bournemouth's Eli Junior Kroupi and Alex Scott, Brentford's Michael Kayode, Newcastle United's Lewis Hall and West Ham's Mateus Fernandes to claim the award by public vote.
O'Reilly has made 34 Premier League appearances this season, scoring five goals and providing three assists. His most memorable moment came at Wembley in March, when he scored twice in the EFL Cup final as City beat Arsenal to claim the trophy. He was named man of the match.
He is the fourth City player to win the award since its inception in 2019 — and becomes the youngest to receive Manchester City's own internal player of the season accolade, which he also won this week. Phil Foden won the Premier League prize in both 2020-21 and 2021-22, with Erling Haaland taking it in 2022-23.
Guardiola has been effusive in his praise throughout the season.
"Nico gives us in the middle that physicality that we need. He is so complete and so young. I am really pleased the academy produced these incredible players."
O'Reilly has also made his senior England debut and is in Thomas Tuchel's 26-man squad for the 2026 World Cup.
City were runners-up in the Premier League this season behind Arsenal, winning the EFL Cup and FA Cup as Guardiola's final act before leaving the club.