Coach Vladimir Petkovic effectively opted for 19-year-old Nico Elvedi, who plays for Bundesliga side Borussia Moenchengladbach, among the central defenders instead of the 31-year-old Senderos.
Senderos, hampered by injuries and a lack of form at club level, returned to the Swiss Super League in January, joining Grasshoppers in search of games after failing to win a place at Aston Villa, who were relegated from the Premier League.
But mistakes in friendly internationals against Bosnia in March and Belgium on Saturday ended his hopes of a place in the squad for the finals in France.
"It's a difficult moment for him," said coach Vladimir Petkovic. "He has maybe lost a bit of confidence and that positive feeling is not there."
Goalkeeper Yvon Mvogo, defender Silvan Widmer and midfielder Luca Zuffi were the other players in the provisional 28-man squad who failed to make the cut, while Renato Steffen has been ruled out with a hamstring injury.
Petkovic had already left captain Gokhan Inler out of his plans due to a lack of playing time at English champions Leicester City following his move from Napoli. Stephan Lichtsteiner will be the skipper instead.
Switzerland have lost their last three friendlies and several of their players have struggled at club level this season while Petkovic has struggled to impose his ambitious attacking philosophy on the team.
Breel Embolo, a 19-year-old striker who plays for FC Basel, and Grasshopppers forward Shani Tarashaj, 21, were included.
Switzerland face Albania, France and Romania in Group A at nest month's finals.
Goalkeepers: Roman Buerki (Borussia Dortmund), Marwin Hitz (Augsburg), Yann Sommer (Borussia Moenchengladbach).
Defenders: Johan Djourou (Hamburg SV), Nico Elvedi (Borussia Moenchengladbach), Michael Lang (FC Basel), Stephan Lichtsteiner (Juventus), Francois Moubandje (Toulouse), Ricardo Rodriguez (VfL Wolfsburg), Fabian Schaer (Hoffenheim), Steve Von Bergen (Young Boys)
Midfielders: Valon Behrami (Watford), Blerim Dzemaili (Genoa), Gelson Fernandes (Rennes), Fabian Frei (Mainz 05), Xherdan Shaqiri (Stoke City), Granit Xhaka (Borussia Moenchengladbach), Denis Zakaria (Young Boys)
Forwards: Eren Derdiyok (Kasimpasa), Breel Embolo (FC Basel), Admir Mehmedi (Bayer Leverkusen), Haris Seferovic (Eintracht Frankfurt), Shani Tarashaj (Grasshoppers)
(Writing by Brian Homewood; Editing by Ken Ferris)
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