The former Leeds United and Luton Town boss saw his side go three goals behind within the opening 23 minutes, leading to a barrage of abuse from the home support.
The game was peppered with raucous renditions of 'Blackwell out' and the man at Bramall Lane helm has now been given the boot.
A statement from the club read: "Following the home defeat to QPR, Sheffield United and Kevin Blackwell have jointly agreed to part company with immediate effect.
"Kevin Blackwell has worked tremendously hard over the last two and a half years and his record in terms of results is equal to, if not better than, most previous managers at Bramall Lane.
"He will always have a warm welcome at Sheffield United.
"However, it is time for us to move on because our ambition remains the same in challenging for promotion, hence this decision to look for a new manager to carry on the work Kevin has been doing."
The 51-year-old took the reins in February 2008 and took the Blades to within a whisker of the Barclays Premier League the following season.