The brains behind the famed educational television show for tots will partner with the agencies in four public service announcements warning children of the need to stifle sneezes, wash hands and to stay home if they get sick.
"Wash with Elmo, wash, wash, wash," the furry red muppet says in one ad, imploring kids to keep their hands clean to stop the spread of germs.
US officials have repeatedly warned of a likely resurgence of H1N1 flu as children return to school over the next few weeks after the long summer break.
"We are thrilled to partner with Elmo, Gordon, and Sesame Workshop again to emphasize the steps kids and their parents can take to stay happy and healthy this school year," said Health and Human Services Secretary Kathleen Sebelius.
"Younger children and their parents are some of the people most at risk from the new H1N1 flu virus.
"With schools starting back up again and the weather starting to get colder, we need to do everything we can to get these important messages about how to prevent the spread of the flu out there."
The new public service advertisements unite the Department of Health and Human Services, the Department of Homeland Security and the Department of Education with Sesame Workshop, the non-profit group behind Sesame Street.
The tie-up was announced by the White House hours before President Barack Obama was set to meet senior US officials in the Oval Office for a briefing on US preparations to combat the flu.
In the government's worst-case scenario the A(H1N1) virus -- which spreads easily among children -- could cause as many as 90,000 deaths in the United States alone.
Since it appeared in April, the virus has infected about two million people nationally, seen 7,983 taken to hospital and 522 deaths.
New US medical advice tells kids to keep their distance from those who are sick, sneeze into their arms to stop germs being spread on their hands, and frequent hand washing with soap and water.
The Mexican version of Sesame Street, Plaza Sesamo, quickly responded to the Mexican swine flu outbreak earlier this year with four similar public service announcements, including several Mexican celebrities.