It was Obama's first trip to the country since he became president 14 months ago.
The brief trip was expected to include a one-on-one meeting with Karzai, an expanded meeting with Karzai's cabinet and US officials, and a speech to American military personnel.
The president left the United States on Air Force One shortly after 10 p.m. EDT on Saturday (0200 GMT on Sunday).
Reporters were taken by bus to the hangar where the plane was kept to maintain secrecy.
White House spokesman Robert Gibbs, speaking before the trip, said Obama wanted to get an "on the ground update" about the war from General Stanley McChrystal, the US and NATO commander, as well as Karl Eikenberry, the US ambassador.
Obama will press Karzai in face-to-face meetings to crack down on corruption and battle drug trafficking as the US military expands its presence in the country and battles the Taleban insurgency.
"We plan to engage President Karzai as we're going to begin, to make him understand that ... in this second term that there are certain things he has to do as the president of his country to battle the things that have not been paid attention to almost since day one," national security adviser General James Jones told reporters on Air Force One.
Jones declined to say that Karzai was falling short in meeting commitments he had made to reform.
In December Obama ordered the deployment of an extra 30,000 US troops to Afghanistan and set a mid-2011 target to begin withdrawal. General Doug Lute told reporters about 10,000 of the 30,000 additional troops being sent to Afghanistan were now on the ground there.
The trip allows Obama to see the early results of his troop increase strategy, show support for military personnel and counter critics who say his focus on passing healthcare legislation has diverted attention from foreign policy.
Obama is expected to greet troops and meet diplomats while in the country.
Obama's domestic victory on healthcare reform last week gives him political space to turn his attention to the Afghan war, which has mixed support from the American public amid rising casualties, costs, and corruption among Afghan leaders.
Obama traveled to Afghanistan during the 2008 US presidential election campaign but has not been back since his victory over Republican Senator John McCain, whose criticism at the time prodded the Democrat's trip.
The White House official said weather and logistical reasons had thwarted previous attempts at a presidential visit since Obama took office in January 2009.
Much has changed during Obama's first year in office.
Top US officials held a multi-month review of the White House's war policy, culminating in the decision to send more troops. When all 30,000 arrive by the end of this year, the number of US troops in Afghanistan will have tripled on Obama's watch to 100,000, along with more than 40,000 from other NATO countries.
Karzai, who remained in power after a fraud-marred election, has launched a high profile effort to reach for reconciliation with the Taleban, who have made a comeback more than eight years since their ousting by US-backed Afghan militias.
US Defense Secretary Robert Gates said last week the timing was still not right for reconciliation with senior Afghan Taleban leaders.
Obama speaks less often to Karzai than did his predecessor, former President George W. Bush, who launched the war in the aftermath of the Sept. 11, 2001, attacks on the United States.
