The Comcast bid is higher than the £19bn Rupert Murdoch’s Fox has offered to buy the 61% of Sky it does not already own.
"As a result of the announcement of this higher cash offer, the independent committee is withdrawing its recommendation of the offer announced by 21st Century Fox on 15 December 2016 and is now terminating the co-operation agreement entered into with 21st Century Fox on the same date," Sky's independent directors said in a statement on Wednesday.
Comcast said its offer of £12.50 per share for Sky represents a 16% premium to Fox’s £10.75 per share proposal.
In a statement, Comcast chief executive Brian Roberts said: "We are delighted to be formalising our offer for Sky today.
"We have long believed Sky is an outstanding company and a great fit with Comcast. Sky has a strong business, excellent customer loyalty, and a valued brand. It is led by a terrific management team who we look forward to working with to build and grow this business."
Comcast had already said in February that it was considering a £22bn bid for Sky so the announcement of the formal offer was expected.
READ: Here’s the news: Sky gets surprise £22.1bn cash bid from Comcast, trumping Rupert Murdoch's Fox offer
Premier League rights a 'game-changer' for Sky's value
George Salmon, equity analyst at Hargreaves Lansdown, said: "Part of the reason the value of the deal is significantly higher than what Fox originally put forward is that Sky has since secured three more years of rights to Premier League football at a reduced cost. As far as the value of Sky goes, that’s a game-changer."
READ: Premier League auction sees rights fees cool, so is the rivalry now over for Sky and BT Sport?
He added: "The rights may come with multi-billion pound price tags, but Sky has proven the Premier League deals are well worth the outlay. The group looks on course to deliver operating profits of £1.5bn this year, double what it earned ten years ago.”
Comcast makes pledges to protect Sky News
Comcast, which owns CNBC, NBC Universal and Universal Pictures, plans to agree a number of legally-binding commitments with regard to Sky News.
It has pledged to keep Sky’s headquarters in London and guarantee the editorial independence and funding of Sky News for at least 10 years. Comcast also said it would not look to buy a majority interest in any UK newspaper for at least five years.
Fox-Sky bid scrutinised by UK regulators
Fox had also made a series of concessions to UK regulators to soothe concerns over its Sky takeover bid, including giving Sky News an independent editorial board and selling the channel to Disney.
The proposed deal was being investigated by the UK Competition and Market Authority over worries it would give Murdoch too much influence over the UK media.
Murdoch owns The Times, Sunday Times and The Sun newspapers in the UK.
The investigation held up a separate US$66bn deal Fox has made to sell its entertainment assets to Walt Disney Co (NYSE:DIS).