The former Director of Public Prosecutions has told the media he expects Sepp Blatter will be questioned as part of the FBI investigation into corruption - possibly under arrest.
Mr Blatter won a fifth term as FIFA president on Friday despite widespread calls for him to resign after seven officials were arrested last week on a US warrant.
The arrests were connected to a bribery scandal being investigated by American, Swiss and other law enforcement agencies.
Lord Macdonald told Sky's Murnaghan programme: "I think the real threat to Mr Blatter doesn't come from the Swiss, it comes from the US, their anti-racketeering legislation and co-operating accomplices.
"Jack Warner, the FIFA man who has been arrested in Trinidad, has already said to the press 'if I'm going down, why isn't he being arrested as well?' referring to Mr Blatter.
"I think the risk to Mr Blatter is this developing investigation in Washington.
"I think the Americans will want to talk to Mr Blatter and they may do it under arrest."
A total of 18 people connected to football have been indicted on corruption charges by the US Justice Department.
Mr Blatter is not named in the US indictment and denies any personal involvement in alleged acts of bribery.
During a news conference in Switzerland on Saturday, he was asked by Sky News if he authorised a $10m bribe to the disgraced official Jack Warner.
"Definitely that's not me. I have no $10m," Mr Blatter replied.
The allegation is contained in the US indictment which states, "a high-ranking FIFA official caused payments... totaling 10 million - to be wired from a FIFA account in Switzerland to a Bank of America correspondent account in New York... controlled by Jack Warner".
When Mr Blatter was asked if he was worried about being arrested in the corruption investigation, he responded curtly: "Arrested for what? Next question."
Meanwhile, Barclays has launched an internal review into whether it was used for illegal payments by FIFA officials, a source told AFP news agency.
It was one of three banks with British headquarters named in the US indictment.
Another, Standard Chartered, said on Friday: "We are aware that two payments cleared by Standard Chartered are mentioned in the indictment. We are looking into those payments."
The third named bank, HSBC, has so far declined to comment.
It comes after Prince William urged FIFA to reform and show "it can represent the interests of fair play".
The Duke of Cambridge, who is president of the Football Association, has asked sponsors to press for changes at FIFA.