The 34-year-old has been sidelined for the past five months due to an Achilles injury but was named in the provisional 28-player squad for the summer tournament.
However, Houghton - who has earned 121 caps for the national team - has been cut from the final 23-player squad after making a mere five Women's Super League appearances throughout the season.
Houghton is one of five players to miss out after their provisional call-ups, with Everton goalkeeper Sandy MacIver also left out of the final squad.
Two-cap Chelsea defender Niamh Charles is the second defender to be cut from the final squad alongside Houghton, while Manchester United duo Lucy Staniforth and Katie Zelem will not be competing at the Euros either.
A star-studded frontline includes the likes of Alessia Russo, Nikita Parris and Chloe Kelly, while Fran Kirby has also held her place despite her lengthy absence in the WSL season due to illness.
Wiegman's side will take on Austria, Northern Ireland and Norway in Euro 2022 Group A and will prepare for the Championships with friendlies against Belgium, the Netherlands and Switzerland later this month.
ENGLAND SQUAD
Goalkeepers: Mary Earps, Hannah Hampton, Ellie Roebuck
Defenders: Millie Bright, Lucy Bronze, Jess Carter, Rachel Daly, Alex Greenwood, Demi Stokes, Lotte Wubben-Moy
Midfielders: Fran Kirby, Jill Scott, Georgia Stanway, Ella Toone, Kiera Walsh, Leah Williamson
Forwards: Bethany England, Lauren Hemp, Chloe Kelly, Beth Mead, Nikita Parris, Alessia Russo, Ellen White