The US Embassy in Khartoum did not name the potential attackers but has said in the past that terrorist groups were active in Sudan.
Embassy staff published a warning late on Friday on their website of "a potential threat against commercial aviation transiting between Juba, Sudan and Kampala, Uganda".
Juba is the capital of semi-autonomous southern Sudan.
"The US Embassy has received information indicating a desire by regional extremists to conduct a deadly attack onboard Air Uganda aircraft on this route," the embassy statement read.
It added it was not clear whether the group had the ability to mount an attack but warned air passengers to be alert.
Last year, the US embassy warned Islamic militants had threatened violence against Sudan's government and could target Western interests following the death of a suspected militant.
US aid official John Granville and his driver Abdelrahman Abbas Rahama were shot dead when returning from New Year celebrations in Khartoum in 2008. Four men described as Islamist extremists were sentenced to death over the attack.
Sudan, which hosted al Qaeda chief Osama bin Laden in the 1990s before expelling him, has been on a US list of state sponsors of terrorism since 1993.
US officials have acknowledged Sudan has been cooperative in sharing intelligence on militant groups since the September 11 attacks in 2001.
The Sudanese government has repeatedly denied al Qaeda has an active presence in Sudan.
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