Byrne has signed a one year deal that will see him a Prenton Park until at least the summer of 2023, he made 40 appearances for Pools last season in League Two.
The defender has joined the League Two rivals for an undisclosed fee, the club has confirmed.
Pools say the move was sparked following a desire from Byrne to move closer to home.
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Byrne is the latest player to leave Pools following the exit of Luke Molyneux, Timi Odusina and Omar Bogle.
Bogle joined Pools in the final week of the January transfer window, signing a two-and-a-half-year deal with the club. However, just five months on and the striker has left the Suit Direct Stadium to join Newport County for an undisclosed fee.
Boss Paul Hartley said: “Everyone at the club would like to thank Neill for his service over the last year.
"After a few conversations with him, he expressed a desire to be closer to home and we wish him all the best.”
Reflecting on his move, Byrne said: “Once I heard there was interest from Tranmere it was a move I really wanted to get over the line.
"With it being so close to my house, my family and my partner's family who are all massive Tranmere fans and so are my friends it’s something I’m really excited about.
“Tranmere is a massive Club with a big fan base.
"I played here last year and all my friends and family came and they were all raving about the size of the stadium, the supporters, the pitch, so as soon as I heard there was interest with it being such a big club it was a move I wanted to make.”
Rovers boss Micky Mellon added: “We are really pleased to bring Neill to Tranmere. He will add experience to our squad and will help with the development of the younger players in the group.
“He’s got the experience that we are looking for and we’re really looking forward to working with him and having him around the squad. His capability and knowledge of the game is something that will really benefit us.”