Best will undergo surgery tomorrow on his ankle injury and he will not play any part in the remaining seven matches.
With 12-goal midfielder Kevin Nolan sidelined for the next two matches through suspension, even more is resting on the shoulders of the forward-thinkers Alan Pardew has left to call on.
Ameobi, who is playing through pain while he plays with a protective mask covering his fractured cheekbone, is one of just three senior strikers Pardew has available.
While Peter Lovenkrands scored in the weekend win over Wolverhampton Wanderers, only the largely untested teenager Nile Ranger provides an alternative.
Ameobi, however, is confident Newcastle have the mental strength to cope and believes fans will see a determined display at Aston Villa on Sunday.
"What's new We've been stretched all the time," said Ameobi, who has had to take on much of the attacking responsibility since Andy Carroll's departure in January.
"We're going to have to deal with it. Kevin is our leading goalscorer as well and he leads by example. But we've got players who can step in and cover, we've shown that all season.
"We lost a big player in January in Andy Carroll, but the strikers have managed to cover for that loss. You need to have a squad if you're going to compete in this league and regardless who is in the starting line up at Villa, we'll compete that's for sure."
Nolan's two-match ban coincides with the final game of the suspension key midfielder Cheik Tiote is serving, while Best has missed the last two games with an ankle problem.
It means Best will also miss Ireland's summer fixtures, having forced himself into contention after scoring six goals in ten Premier League starts since Carroll last played for the club.
It is not so much Best's injury which concerns Lovenkrands, however, but the Dane admits the loss of Nolan is a blow.
Nolan could still travel with the squad to Villa to keep morale high and Lovenkrands thinks he is under-rated.
"I don't know why, but he is," said Lovenkrands. "When you think of some of the players who have been picked by England, that he has not even had a look in, it's incredible.
"Last year and this year he has scored goals from midfield like Gerrard and Lampard does. They are the only two really who do it as often as him. I don't understand why he does not get the chance to prove himself at that level.
"He is such a good pro, such a good player and such a good character to have in the dressing room, so it's strange."
In fact neither Gerrard nor Lampard come near to his tally this season, with Dimitar Berbatov (20) and Carlos Tevez (19) the only two to have scored more than the Newcastle captain in the league.
His last arrived in the victory over Wolves, when he opened the scoring after Ameobi's flick on put him clean through with goalkeeper Wayne Hennessey.
Lovenkrands, who has five goals himself, said: "Kevin did that even though he was struggling with flu. Yet he went out on Saturday, still struggling, bursts through and gets our first goal.
"That is what we need our captain to do. He is fantastic in that role. It's vital to our dressing room that we have someone like Kevin."
n Newcastle have announced their third pre-season fixture in the United States with a friendly with Orlando City on Saturday, July 23.
United will spend a couple of days training in Florida before taking on the Lions, whose head coach is former Everton, Manchester City and Burnley midfielder Adrian Heath.
The match will complete the Magpies' trip to the States, with games either side for Alan Pardew's team, who will also take on Sporting Kansas City on Wednesday, July 20, and Columbus Crew on Tuesday, July 26.