The crash was reported at 10:23 a.m. at the intersection of Third and 23rd streets, Muni spokesman Paul Rose said.
The collision caused minor injuries to six people on board, San Francisco Fire Department spokeswoman Lt. Talmadge said.
The victims were taken to a hospital and are expected to survive, she said.
The Muni light-rail vehicle was on the KT-Ingleside/Third Street line.
Rose said the truck hit the Muni car on its right side, toward the front of the vehicle.
"We're working with the Police Department to determine exactly what happened," he said.
An employee at the nearby Ameritech Computer Service, Inc., located at 2688 Third St., said a truck with a flatbed trailer T-boned the Muni vehicle.
He said he didn't hear the crash happen, but came outside afterward and saw several people being put into ambulances on stretchers.
Bus shuttles took passengers around the area while crews worked to clear the scene.
The crash was cleared at 11:25 a.m. and normal Muni service resumed. .