Authorities placed the campus in Harris County on lockdown following reports of gunfire on campus, the Houston Chronicle reported.
According to CNN, two students were shot in the crossfire between two gunmen. One gunman was hit and taken into custody, and the other left campus.
Medics could be seen tending to at least two victims outside the school, KTRK reported.
A fourth person suffered a heart attack on scene, according to CNN.
A possible second gunman is being sought, The Associated Press reported.
The campus has been evacuated, and buses were brought in to remove students from the area, according to KTRK.
The school shooting, which wasn't the first in the United States this month, came on the heels of protests in New York by the group One Million Moms for Gun Control, which was founded in the wake of December's shooting of 26 children at Sandy Hook Elementary School in Newtown, Conn.
Student Cody Harris, 20, told the AP he was in psychology class with about six or seven other students when he heard eight gunshots.
"I was just worried about getting out," he said. "I called my grandmother and asked her to come pick me up."
According to AFP, the college posted a warning to students on Facebook: "SHELTER IN PLACE if you are on campus. IF YOU ARE NOT ON CAMPUS DON'T GO TO CAMPUS."'
Several public schools in the vicinity were also on lockdown.
The Lone Star College System has an enrollment of 90,000 students and six college campuses, according to its website.
More than 10,000 students are at the North Harris campus, spokesman Jed Young told CNN.