Stuart Monkcom, the chairman of leader Paul Nuttall's own branch in Liverpool, and Adam Heatherington, chairman of the Merseyside regional branch, comments made by party figures had been "upsetting and intolerable" for the victims of the families.
The announcement is another blow to Mr Nuttall just days before the Stoke-on-Trent Central by-election where he is hoping to oust Labour.
He has already had to apologise for a statement on his website falsely claiming he lost "close friends" in the disaster in which 96 Liverpool fans died.
The party's millionaire backer Arron Banks caused further anger when he said he was "sick to death" of hearing about Hillsborough and accused critics of Mr Nuttall of "milking" the disaster for political purposes.
In a statement, Mr Monkcom said: "Although the timing of our resignations is unfortunate in light of upcoming elections both Adam and I wish to make it clear where the painful subject of Hillsborough is concerned, with closure not yet in sight, this unprofessional approach and crass insensitivity from high-profile people closely within and without Ukip is upsetting and intolerable.
"We identify most strongly with all the good people of Liverpool and most importantly the families of the Hillsborough victims, who have fought so long and hard for justice in their condemnation of the way Ukip has handled these issues and have resigned our positions and membership of Ukip forthwith."