"We are hopeful, but based on past experience also skeptical that in fact the separatists will follow through and that Russia will stop violating Ukraine's sovereignty and territorial integrity," Obama said.
"It has to be tested."
To maintain Western pressure, he said, the U.S. and Europe are finalizing measures "to deepen and broaden our sanctions across Russia's banking, energy and defense sectors."
Those new sanctions could be lifted if the cease-fire and a peace deal are successful in ending the fight between Ukrainian troops and pro-Russia separatists.
The president also praised the firmness by the Western alliance in confronting Russia, including the creation of a new rapid response force to defend NATO members in Eastern Europe.
He said it underscored the principle that "big countries just can't stomp on little countries."
The conditional cease-fire agreement, which was signed Friday in Minsk by Ukraine, Russia, pro-Russia separatists and the Organization for Security and Cooperation in Europe, took effect Friday afternoon.
Heidi Tagliavini of the OSCE told reporters the deal focused on 12 separate points but she did not immediately spell them out.
Ukrainian President Petro Poroshenko said a prisoner exchange would begin Saturday and international monitors would keep watch over the truce.
"The highest value is human life. We must do everything possible and impossible to terminate bloodshed and put an end to people's suffering," Poroshenko said in a statement announcing the agreement.
NATO Secretary-General Anders Fogh Rasmussen said he would "warmly welcome" the establishment of a real cease-fire.
"But it is one thing to declare a cease-fire," he said.
"The next and crucial step is to implement it in good faith and it remains to be seen. But so far so good."
Earlier, Rasmussen, in announcing approval of the rapid-response force by the 28-nation alliance, said it would send a clear message to potential aggressors.
"Should you even think of attacking one ally, you will be facing the whole alliance," he declared as the two-day NATO summit in southern Wales drew to a close.
Ukraine, however, is not a full member of NATO.
Rather, it is a "partner," which means it cooperates on a range of issues with the alliance, including receiving some military assistance.
The partner status means that overt military intervention by NATO against Russia for its actions in Ukraine is extremely low because there is no enshrined commitment to do so.
Rasmussen said the quick-response force would give NATO a "continuous presence" in Eastern Europe, with alliance countries contributing forces on a rotational basis.
Marshall Bradley Webb, a U.S. Air Force lieutenant general who currently serves as commander of NATO's Special Operations, a unit that will support NATO's ambitions to react more quickly to security threats, described NATO Special Operations as "the new kid on the block."
He said the unit is "rapidly deployable, agile" and can be activated "at a moment's notice."
He spoke to journalists in Wales, where NATO was demonstrating its hybrid Osprey aircraft that can fly like a plane but land like a helicopter.
Rasmussen also said allied countries feel a new urgency to meet a long-sought goal of spending 2% of their GDP on defense and security.
"Russian aggression against Ukraine is a wake-up call," he said, adding that for NATO countries "it is now obvious that we cannot take our security for granted."
The United Nations estimates that more than 2,600 people have been killed since the conflict began in April.
Washington and Europe have warned Russia that if the crisis in Ukraine continues it may face further sanctions.
On Thursday night, NATO leaders also discussed at a working dinner the threat posed by the militant group Islamic State.
"Our message is clear: We are united in condemnation of these barbaric acts," said British Prime Minister David Cameron, referring to the beheading or two American journalists.