Frank de Boer, the Netherlands coach, will not call up a replacement for the 24-year-old. The nature of Van de Beek's injury has not been made public.
A statement from the Dutch Football Association said: "Donny van de Beek is not available to play the European Championship with the Netherlands. The Manchester United midfielder is struggling with an injury. As a result, the 19-time international, who last played for the Dutch squad in March, is not fit enough to join for the tournament."
Netherlands and PSV Eindhoven right-back Denzel Dumfries said: "This is a huge blow. As a group we are working towards the tournament and Donny is part of our group. We all really feel for him."
It's the latest setback in what has been a difficult year for Van de Beek, following his move from Ajax to Manchester United last summer. He made just four starting appearances in the Premier League last season, scoring once.
Manchester United manager Ole Gunnar Solskjaer has continually played down suggestions that the player is unhappy at failing to make a breakthrough at Old Trafford.
"I've answered this question so many times and there's so many examples of players needing a little bit of time, quality players," Solskjaer said.
"We have many examples ourselves and there are other clubs with examples and sometimes it takes time."