Willian Jose socred the only goal of the game at Molineux to earn a 1-0 win for Nuno Espirito Santo’s side and consign their opponents to a fate which has seemed inevitable for some time.
The result was the Blades’ 26th league defeat of the season and leaves them 19 points adrift of safety with just six games left to play.
Sheffield United took the top flight by storm last season, having risen from League One with two promotions in three years.
They have struggled badly this season, though, and went 17 games without a win at the start of the campaign, picking up just two points in that run.
They finally tasted victory for the first time this season against Newcastle on January 12 and showed signs of a resurgence, winning two of their next four games.
However, they have won just once more since and manager Chris Wilder left the club by mutual consent last month.