As Congress debates whether to approve President Barack Obama's call for a military strike against the regime of Syrian President Bashar Assad, which the U.S. administration holds responsible for an Aug. 21 chemical weapons attack that killed more than 1,400 people, McDonough said fears of an extended occupation should be put to rest.
In an appearance on CNN's "State of the Union," McDonough said he understands the fear the United States might get "dragged into the middle of an ongoing civil war," but he said officials plan to "be very careful and very targeted and very limited in our engagement."
"This is not Iraq or Afghanistan. This is not Libya," McDonough said. "This is not an extended air campaign. This is something that's targeted, limited and effective, so as to underscore that [Assad] should not think that he could get away with this again."
McDonough said on CBS' "Face the Nation" that Americans "learned our lesson" in getting heavily involved in Iraq. A military strike on Syria wouldn't escalate into a nine-year war as Iraq did.
"The president opposed Iraq because he knew it was an inchoate mission with unplanned for consequences, unbudgeted for costs, and we saw the result of that," McDonough said. "And that's why the president undertook the effort that he did with our military leadership to end that war."
In an appearance on "Fox News Sunday," McDonough said Obama isn't concerned with whether a rejection of the measure by Congress would affect his ability to lead for the last three years of his presidency.
"Politics is somebody else's concern," he said. "The president is not interested in the politics of this. The president is interested in making sure that our national security is protected. That's the question, first and foremost, for us."
During an appearance on ABC's "This Week," McDonough said the question before Congress "is a very simple one -- should there be consequences for [Assad] having used gases, chemical weapons, to kill more than 1,000 of his own people, including more than 400 children?"
"The answer to that question will be followed closely in Tehran ... the answer to that question will be followed closely in Damascus, the answer to that question will be followed very closely by members of Lebanese Hezbollah," McDonough said.
Failure to retaliate for the use of chemical weapons would mean "a greater risk of them being proliferated" and perhaps falling into terrorists' hands, McDonough said on NBC's "Meet the Press."
"Our troops have not been subject to chemical weapons attacks since World War I," he said. "We have to make sure that for the sake of our guys -- our men and women on the front lines -- that we reinforce this prohibition against using chemical weapons."
The Senate could vote on a possible military strike as early as Wednesday. The measure needs 60 votes to move ahead to final passage.