Heckingbottom is the first Premier League managerial casualty this term, Wolverhampton Wanderers parted ways with Julen Lopetegui three days before the start of the season.
The club confirmed the news on Tuesday in a statement: "Sheffield United can confirm that football manager Paul Heckingbottom has been relieved of his duties. Additionally, coaches Stuart McCall and Mark Hudson, have also left the club."
The club confirmed the news after a poor start to the season with just five points and one win in 14 games to leave them bottom of the Premier League.
Prince Abdullah Bin Mosaad Bin Abdulaziz Al Saud, the owner of Sheffield United, revealed the news on Talksport radio on Tuesday morning, as well as announcing Heckingbottom's predecessor Chris Wilder as his replacement.
"Yes [I have made the decision]," Prince Abdullah told Talk Sport.
Heckingbottom took charge of United in 2021, leading them to promotion back to English football's top flight last season after they finished second in the Championship.
Heckingbottom becomes the first Premier League manager to lose his job this season in a change to recent campaigns. There were 14 managerial changes last season and 10 the year before.
"I have mixed emotions about letting Paul go," Prince Abdullah told Talksport. "I really have a lot of respect for Paul and everything he did for the club, he's a very classy guy.
"But I felt like after the last few games it was a necessary decision and the replacement has done great things for the clubs and knows the club, so I feel good about the decision in one way but I really have a tremendous respect for Paul."
Discussing Wilder's return, Prince Abdullah said: "Chris [Wilder] is practically an honorary of the club, he's part of Sheffield United history.
"Chris has done great things for the club and in my opinion he's the best guy on planet earth to take over the club right now in these circumstances."
In his previous stint with Sheffield United, Wilder took over when the club was in League One and earned two promotions, returning them to the Premier League for the first time in 12 years in 2019.
In their first season back in the top division, Sheffield United finished ninth -- winning Wilder the LMA Manager of the Year award for 2019-20.
However, the following season saw Wilder's team fail to win a Premier League game until the 18th match of the season and he was sacked in March 2021.
On Tuesday, Wilder told his players to treat Wednesday's Liverpool match as if it were a cup tie.
"I'm under no illusions that it's an incredible first game to be involved in but we have the lift of 33,000 at Bramall Lane under the lights," Wilder said at a news conference.
"It's not a great situation, everybody knows that. It is the best league in the world and we are playing Liverpool first game up, so thanks very much for the fixture list.
"I said to the players, 'look at it this way, this is a third-round FA Cup tie, what would your approach be?'.
"You would be looking forward to it, you would want to go and get amongst it and you would want to prove a point and go and get a big result."
Wilder took United from League One to the Premier League in his previous spell as manager at the club, and does not believe in the phrase "never go back."
"There's enough examples of other managers that have gone back and enjoyed their time," Wilder said.
"I'm more enthusiastic and determined than I've ever been in my life. I think Sheffield United are getting me at my best. At times you have to feel the failure and feel the pain to make you better, and I certainly have.
"There's a reason why [club owner] Prince Abdullah wants me to come back to the football club. Regardless of what other people will feel and think, he thinks I'm the best man to do the job and I'm delighted he thinks that."
Wilder is determined to prove that their season is far from over.
"We are up against it, everybody in the world, every pundit that wants to make an opinion, every supporter, they all think we are done and dusted.
"It's going to be a long, hard season, we understand that.
"There are going to be some difficult moments and we are going to have to suffer, but hopefully we can get a reaction out of the players and help them because, obviously, at the moment confidence is very low."