Former Hibs boss Paul Heckingbottom
Heckingbottom, who had a spell as Blades caretaker manager last season, has agreed a contract until the end of the 2025-26 season.
Jokanovic’s dismissal came after just six months in the role. The Serbian, who had signed a three-year contract, won only six of his 19 league games in charge and United remain 16th in the table, eight points off the play-off places, despite Tuesday's 1-0 victory at Reading.
A statement on the club's website read: "Following several months of strategic planning and a lacklustre start to the season, the board decided that a change was in the best long-term interests of the club."
Heckingbottom, who has also managed Barnsley and Leeds as well as Hibs, will be in place for Sunday's Championship visit of Bristol City.
Chairman Yusuf Giansiracusa said: "We look forward to embarking on a new era in Blades football with Paul at the helm. Paul possesses the personal leadership qualities and technical football skills the board feels are essential to successfully implement the board's strategic directives.
"He shares our values and interest in player development while also possessing the ambition and determination to get the most out of our current squad. We are convinced that Paul will play a leading role in improving all aspects of football operations."
Heckingbottom will be joined at the club by former Motherwell and Rangers boss Stuart McCall, who will be his assistant manager.
Hibs brought in the Englishman as head coach in February 2019 to succeed Neil Lennon and he made a good start, winning the Premiership Manager of the Month award for March 2019 and then beating Hearts at Tynecastle in his first Ediburgh derby.
After finishing fifth, Heckingbottom made a poor start to the new campaign with only one win from 11 in the league.
Heckingbottom was sacked in November 2019 following a 5-2 defeat by Celtic in the Betred Cup semi-final, with the team 10th in the table.
He oversaw 32 games as Hibs head coach, winning 12, drawing 11 and losing nine.