Chief warrant officers Jefferson Williams and Lewis Welshofer Jr, Sergeant 1st Class William Sommer and Specialist Jerry Loper could get life in prison without parole if convicted of the November 2003 death of Major-General Abid Hamid Mawhush, 57, in Qaim, Iraq.
The US army at Fort Carson in Colombus said on Monday Welshofer was part of a two-person interrogation team that questioned Mawhush.
In May, the US army said the Iraqi general was asphyxiated by chest compression and smothering.
Mawhush, a member of the now disbanded Republican Guard's air defence branch, was captured in a raid in Qaim.
A US military spokeswoman said at the time that Mawhush was believed to have been financing attacks on US forces.
The charge against the four is the latest in a series of similar cases involving US troops.
Some US soldiers have been
charged with murdering Iraqis
In September, a US soldier was sentenced to 25 years in jail for the murder of a member of the US-established Iraqi national guard the previous May.
Specialist Federico Merida, found guilty of murder in the town of al-Dawr near Tikrit, was handed one of the heaviest sentences for a US serviceman since the start of the US-led invasion of Iraq.
Prior to that, two US soldiers serving in Iraq were charged with premeditated murder in connection with the deaths of three Iraqi civilians.
Dereliction of duty
The soldiers charged were Sergeant Michael Williams and Specialist Brent May, both members of the 1st Cavalry Division, operating in and around Baghdad, but normally based at Fort Riley in Kansas.
Earlier, US army Captain Rogelio Maynulet, a 29-year-old from Chicago, was charged with murder and dereliction of duty in the 21 May death of a driver of Shia leader Muqtada al-Sadr.
Maynulet has since denied the charge and the case is before a military court at a US base in Germany.