The Nigel Twiston-Davies-trained Bristol De Mai has landed the £200,000 contest in each of the last two seasons and will bid to become the third three-times winner on November 23.
The legendary Kauto Star claimed the prize four times between 2006 and 2011, while Cue Card completed his hat-trick between 2013 and 2016.
Twiston-Davies said: "Bristol De Mai is in good form. Everything is fine with him and we decided to head straight for Haydock.
"We did it last year and it worked well, so hopefully things can go well again this time around.
"He had a great season last term and we were delighted with his third in the Gold Cup. Hopefully, he can continue improving this term."
Bristol De Mai could be joined by his Charlie Hall Chase-winning stablemate Ballyoptic.
"Ballyoptic has come out of the Charlie Hall fine. We were always going to enter him in the Betfair Chase after that victory and he could also run," the Naunton handler added.
Altior is unbeaten in 19 starts over jumps and trainer Nicky Henderson has already declared his intention to step the dual Queen Mother Champion Chase hero up in trip this season. However, it is considered unlikely he will make an appearance on Merseyside with a race at Ascot on the cards instead.
Henderson has also entered Might Bite and Valtor, while Paul Nicholls - who has dominated the Betfair Chase with six victories in total - could this year saddle Frodon and Black Corton.
Precautionary entry for Altior
Speaking in his Unibet blog, Henderson said: "I have been inundated with calls from so many people with regards to Altior being entered in the Betfair Chase at Haydock, so I would like to assure everyone that he is only in there as a reserve in case anything unfortunate, God forbid, should happen at Ascot on the same day.
"We are not running scared of Cyrname, but if for some unusual reason the going came up very heavy at Ascot and it was good at Haydock, then we would seriously have to think about it, but at the moment we are going to run in the Christy Chase.
"We would be looking pretty silly if Ascot was abandoned or anything like that and we weren't even entered at Haydock so we've got to keep our options open, otherwise you can easily get caught out.
"It is purely a precautionary back up just in case. I am very happy with Altior and looking forward to getting him started for the season."
Cue Card's trainer Colin Tizzard is seeking a fourth victory in the race and has entered Lostintranslation - so impressive on his reappearance at Carlisle this weekend - as well as Charlie Hall runner-up Elegant Escape.
An Irish-trained horse has yet to win the Betfair Chase, but there are two possible raiders this year in Henry de Bromhead's Balko Des Flos and the Noel Meade-trained Tout Est Permis, who both carry the colours of Gigginstown House Stud.
