Vaughan, who led England to a memorable Ashes triumph on home soil last year, is to undergo a fourth operation on his longstanding knee injury on Monday that means he will miss the upcoming Test series against Pakistan.
He will be sidelined for between four to six months and given the Ashes campaign starts in November, Vaughan's hopes of making the trip now appear remote.
Flintoff, 28, currently out with an ankle problem, led an inexperienced England team to a 1-1 Test series draw in India earlier this year before overseeing the same scoreline in their home campaign with Sri Lanka.
His only captaincy rivals, assuming he regains fitness, appear to be opening batsmen Marcus Trescothick, skipper in Pakistan before returning early from India for personal reasons, and Andrew Strauss, currently in charge of an England team facing a potential 5-0 One-day series whitewash against Sri Lanka heading into Saturday's Headingley climax.
But Botham was adamant fellow all-rounder Flintoff, who starred in England's victorious 2-1 Ashes triumph last year with 402 runs and 24 wickets, was the leading candidate.
"He deserves to captain England in Australia because he has done it the hard way," Botham said.
"He has the respect of his own players and the opposition players and he has done it by performing," added the England great, who was speaking at a charity event in Manchester earlier this week to raise money for grassroots cricket.
"He is the obvious choice. There is no-one else. If Michael Vaughan isn't fit and doesn't make the trip, it's got to be Fred (Flintoff)."
Many have pointed to Botham's own unhappy experience of the England captaincy in the early 1980s as an example of the dangers of overloading a team's star all-rounder with the extra responsibility of leadership.
But Botham countered: "For those people who say 'what about the burden?' I have got one very simple question. If you are playing against England who would you least like to be tossing in the middle with you?
"He (Flintoff) is the most inspirational figure in the side and if Michael Vaughan - who is the best captain - isn't available then you want the most influential player to be the one calling the shots.
"People try to be detrimental towards him by drawing a comparison with me. They say when Botham was England's leading all-rounder it affected his form but the fact is I lost 1-0 and 2-0 in five-match Test series to a West Indies team that was probably the most powerful of all time.
"Whoever tosses the coin with Ricky Ponting in Brisbane on November 23 can only be one of two people: either Michael Vaughan, if he makes a speedy recovery, or Fred (Flintoff).
"There is no-one else and deep down the England hierarchy must know that."