The US embassy in Islamabad spent about $70,000 to run the announcement, which features clips of Obama and Clinton underscoring U.S. respect for religion and declaring the U.S. government had nothing to do with the movie, it said.
"In order to ensure we reached the largest number of Pakistanis, some 90 million as I understand it in this case with these spots, it was the judgment that this was the best way to do it," State Department spokeswoman Victoria Nuland told a news briefing.
The U.S. announcement aired as Washington warned Americans to avoid non-essential travel to Pakistan, one of the mostly Muslim countries hit by a wave of anti-American demonstrations. In Libya, a deadly assault last week killed the U.S. ambassador and three other Americans.
The protests, which were sparked by an Internet video that mocked the Prophet Mohammad and swept through Yemen, Egypt and other countries, also prompted the U.S. government to withdraw non-essential personnel in Tunisia and Sudan.
In Pakistan, protesters have demonstrated in more than a dozen cities.
Counter-terrorism analysts for the New York Police Department warned in a paper circulated on Thursday that the anti-U.S. and anti-Western protests would continue to spread, fueled most recently by a French magazine's publication of cartoons lampooning the Prophet Mohammad.
The cartoons in France's Charlie Hebdo satirical weekly have provoked relatively little street anger thus far, although about 100 Iranians demonstrated outside the French embassy in Tehran.
Nuland said the decision to buy the television ads, identified as paid public service announcements, was not unusual in countries where this is "the norm for getting your message out."
"I think the sense was that this particular aspect of the president and the secretary's message needed to be heard by more Pakistanis than had heard it, and that this was an effective way to get that message across," she said.
She said it would take time to measure the effectiveness of the ads in Pakistan, where on Thursday huge crowds again gathered to protest against the video.
(Reporting by Andrew Quinn and Mark Hosenball; editing by Warren Strobel and Mohammad Zargham)