The Ukrainian superstar has enjoyed a 10-year title reign at the top of boxing's glamour division but will now put his WBA, WBO, IBF and IBO belts on the line against the undefeated Jennings at the legendary Madison Square Garden in New York.
Klitschko will return to fight on US soil for the first time since February 2008, with the bout set to have high British interest with Manchester heavyweight Tyson Fury mandated to fight the winner later this year.
Overcoming Jennings will be no easy task for 39-year-old Klitschko, with the Philadelphian, who has a three-inch reach advantage, hoping to become the first unified American heavyweight champion in more than 13 years.
After building up an unbeaten record of 19 straight wins, 10 coming by way of knockout, Jennings is confident that he can finally become the man to dethrone Klitschko, who has won 63 fights, 53 by knockout, with only 3 losses - the last coming over a decade ago.
"I do have great respect for Bryant Jennings and his achievements. He has good movement in the ring and good technique. I know this will be a tough challenge," said Klitschko.
"I am extremely happy to fight in New York City again. I had my first unification fight there and a lot of great heavyweight matches have taken place at Madison Square Garden. It will definitely be a great fight night and I will do everything for it from my side," he added.
Jennings has been in equally buoyant mood ahead of the fight and said: "On April 25th history will definitely be made and it will be made by me. One of us has to lose and it isn't going to be me. Enough of the talking, I'm ready to fight."
Jim McMunn, Managing Director of BoxNation, stated: "We are extremely pleased to be able to bring BoxNation subscribers this enthralling fight.
"There is always something special about the heavyweights and given the British interest in this fight, with Tyson Fury up next for the winner, it will be a very intriguing and exciting match-up. Wladimir Klitschko has been pound-for-pound one of the very best for so long but in Bryant Jennings he faces an undefeated and highly-skilled contender that is coming to win."
'The Champion Returns' bill will also see one of boxing's emerging stars in the unbeaten Sadam Ali (below, right) take on the quick handed Francisco Santana as the co-feature in a 10-round welterweight clash.
BoxNation offers real value-for-money for fight fans, with a number of high-profile bouts coming up live and exclusive on the channel with light-welterweight kingpins Danny Garcia and Lamont Peterson facing-off plus Andy Lee vs Peter Quillin on April 11, followed by a night to remember on April 18 with three back-to-back live fights.
Those include Liverpool lightweight Derry Mathews challenging Richar Abril for the WBA world title, with rising superstar Terence Crawford looking to become a two-weight champion against Thomas Dulorme, before the war between punchers Matthysse and Provodnikov.
Those are followed by Klitschko v Jennings on April 25, before the huge battle in front of 40,000 fans at the iconic Minute Maid Park baseball ground between Canelo and Kirkland.