No specific cause of ulcerative colitis has been identified. Although no organism (virus, bacteria, or fungi) has been found to set off the cycle of inflammation that occurs in ulcerative colitis, some researchers continue to suspect that some such organism is responsible for initiating the cycle. Other researchers are concentrating on identifying some change in the cells of the colon that would make the body's immune system accidentally begin treating those cells as foreign invaders. Other evidence for such a disorder of the immune system includes the high number of other immune disorders that tend to accompany ulcerative colitis.

The first symptoms of ulcerative colitis are abdominal cramping and pain, a sensation of urgent need to have a bowel movement (defecate), and blood and pus in the stools. Some patients experience diarrhea, fever, and weight loss. If the diarrhea continues, signs of severe fluid loss (dehydration) begin to appear, including low blood pressure, fast heart rate, and dizziness.

Severe complications of ulcerative colitis include perforation of the intestine (in which the wall of the intestine develops a hole), toxic dilation of the colon (in which the colon become quite large in diameter), and the development of colon cancer.

Intestinal perforation occurs when long-standing inflammation and ulceration of the intestine weakens the wall to such a degree that a hole occurs. This is a life-threatening complication, because the contents of the intestine (which under normal conditions contains a large number of bacteria) spill into the abdomen. The presence of bacteria in the abdomen can result in a massive infection called peritonitis.

Toxic dilation of the colon is thought to occur because the intestinal inflammation interferes with the normal function of the muscles of the intestine. This allows the intestine to become lax, and its diameter begins to increase. The enlarged diameter thins the walls further, increasing the risk of perforation and peritonitis. When the diameter of the intestine is quite large, and infection is present, the condition is referred to as "toxic megacolon."

Patients with ulcerative colitis have a significant risk of developing colon cancer. This risk seems to begin around 10 years after diagnosis of ulcerative colitis. The risk becomes statistically greater every year:

• At 10 years, the risk of cancer is about 0.5–1%.
• At 15 years, the risk of cancer is about 12%.
• At 20 years, the risk of cancer is about 23%.
• At 24 years, the risk of cancer is about 42%.

The overall risk of developing cancer seems to be greatest for those patients with the largest extent of intestine involved in ulcerative colitis.

Patients with ulcerative colitis also have a high chance of experiencing other disorders, including inflammation of the joints (arthritis), inflammation of the vertebrae (spondylitis), ulcers in the mouth and on the skin, the development of painful, red bumps on the skin, inflammation of several areas of the eye, and various disorders of the liver and gallbladder.