Che Adams scored twice and Danny Ings netted from the penalty spot as Saints claimed a comeback win over the Blades at St Mary's.
Ings began the game in the hunt for the Premier League golden boot, and with five minutes remaining, he moved to within one goal (22) of eventual topscorer, Leicester City's Jamie Vardy (23).
The Southampton striker had his opportunities to draw level with compatriot Vardy in the second half, but his selfless approach created better chances for his team-mates.
John Lundstram had opened the scoring from close range for Sheffield as the visiting Blades controlled the first half.
Victory for the Saints sees them end the season in 11th place, while Sheffield United drop to ninth in the table - still their highest finish in the Premier League era.