Khawaja made just a single in Australia's 303 for three on day one at Emirates Old Trafford before he fell victim to a controversial ruling by third umpire Kumar Dharmasena, after his on-field colleague Tony Hill had given the number three out caught-behind off Graeme Swann.
Australian Prime Minister Kevin Rudd Tweeted within minutes that it was the worst decision he had ever seen, and Shane Warne described the verdict as "absolutely shocking" in his television commentary.
Khawaja's apparent misfortune was the latest in a series of DRS controversies which have blighted this summer's Ashes.
Sutherland responded, as did the England and Wales Cricket Board after Jonathan Trott was also controversially given out lbw via DRS in the first Test at Trent Bridge last month, by calling the world governing body to account over how the procedure was used in this instance.
Cricket Australia Tweeted: "CA chief executive officer James Sutherland seeks clarification from the ICC on the dismissal of Usman Khawaja."
Sutherland added in a statement to the press following the close of play: "Cricket Australia has sought an explanation from the ICC on the dismissal of Usman Khawaja. In our view, the on-field decision and referred decision using DRS were both incorrect.
"CA remains a strong supporter of DRS and believes it is important that cricket continues to improve and build confidence in the DRS.
"We understand and accept that from time to time mistakes can be made, however in this instance, on behalf of the player, the team and all cricket fans, we feel duty bound to seek further explanation as to how this decision was arrived at."
Australia opener Chris Rogers was batting with Khawaja when the decision was made and admitted it had left "another question mark" over the DRS.
"I was (surprised). I was at the other end and even in real time I didn't think he hit it," he said.
"I didn't think he was anywhere near it. The umpire must have had a different view on it.
"I thought it was not out and that's why we reviewed it.
"From what we saw on the replay I think even the England guys had given up hope of it being out.
"It was disappointing and another question mark.
"It's a weird thing because it is people's careers on the line. You want these decisions to be right.
"I felt for him but it's been happening so we just have to get on with it. We can't worry about that."
Asked if the players were losing confidence in the DRS Rogers, who hit his Test-best 84, added: "That's a hard one to answer.
"I still think it is important. We want technology to make sure these decisions are correct and sometimes it goes for you and sometimes it goes against you. You just have to take it."