The Guardsmen, from all over Northern California, boarded C-17 cargo planes around 5:00 p.m. The huge aircraft are able to fly non-stop from Moffett Field to Afghanistan, but it may touch down in Europe before it heads off to its final destination.
It is Airman Darren Gray's second time and saying goodbye does not get any easier.
"Mixed emotions... There's a lot to leave and there's a lot of reasons to go. You're kind of torn between your family and your duty to your country," he said.
Pilots, aircrew members, maintenance technicians and support personnel were all onboard for the mission. Their primary duty will be combat search and rescue. Lieutenant Colonel Steve Butow is the group's deputy commander. He says they are all well-trained and prepared to go.
"What we do, as opposed to the ground forces… Because we can fly, we can get places rapidly and get in and out very quickly. And, we set the conditions for our own success," he explained.
The cargo planes will also carry three combat search and rescue helicopters to Afghanistan. Each one is worth more than $9 million and able to recover downed or stranded crews in a war zone.
This week president Obama will meet with the presidents of Afghanistan and Pakistan in a summit in Washington. Even with Washington's renewed focus on the region, University of San Francisco Professor Patrick Hatcher says it will be difficult to measure success there.
"It is not going to be any kind of immediate success and it's likely not to be any kind of thing Americans call success. The best I think we can hope for is a kind of compromise," he said.
The loved ones saying goodbye understand the dangers all too well.
"I just don't want my dad over there because it's really dangerous over there. You never know what's going to happen," said Dorian Broome whose father is Guardsmen.
It is impossible to fully train for an effort like this, but the Guardsmen heading to Afghanistan have helped fight fires in California last year. They also helped with rescue efforts during Hurricane Ike. They hope experiences like those help when they are on the ground in Afghanistan.