The visit coincided with the third anniversary of the country's independence, and the actress said she saw trauma that was "unbearable to comprehend".
She said: "I had no idea what to expect when I arrived in South Sudan, but what I saw and heard was worse than I could have ever imagined.
"All of those I met were suffering a terrible trauma unbearable to comprehend. I spoke to women who have lost their husbands and children within months of one another.
"They are now alone trying desperately to get through each day struggling to provide enough food and water to keep them and their remaining children alive."
Knightley traveled to Bor camp, Jonglei State, which is one of the most affected areas of South Sudan. Poor sanitation means that many lives are taken through the spread of disease, which gets worse with seasonal heavy rain.
The 29-year-old added: "The people I met are facing a relentless crisis of war, hunger and disease.
"I saw the amazing work Oxfam are doing day in and day out to ensure that people have safe water to drink, and food to eat, but the situation is getting worse and resources are running out.
"I met just a few of the thousands of families who are desperately trying to survive each day but they can't do it alone, they need our help."