Chris Porter, Ched Evans and a Danny Webb own goal sealed victory for the Blades before Lloyd Mackie struck a late consolation.
United defender Neil Collins had a header blocked on the line in the 10th minute before Porter latched onto Lee Williamson's pass eight minutes later to side-foot underneath the body of goalkeeper Mark Scott.
After a host of missed chances, the home side doubled their lead on the hour mark when Kevin McDonald's goal-bound effort flicked in off Evans. Steve Simonsen saved comfortably from substitute Macklin at the other end before the Blades made it three on 72 minutes.
Evans skipped past Ryan Brett on the right and his low cross was turned into the net by Salisbury defender Danny Webb.
The Wiltshire side were rewarded for their hard work on 86 minutes when Macklin found space 25 yards from goal to drill into the bottom left-hand corner.