It was the first Titan booster to feature large solid rocket motors and was planned to be used as a launcher for the Dyna-Soar, though the spaceplane was cancelled before it could fly.

The majority of the launcher's payloads were DoD satellites, for military communications and early warning, though one flight (ATS-6) was performed by NASA.

Designated as LGM-25C, the Titan II was the largest USAF missile at the time and burned Aerozine 50 and nitrogen tetroxide (NTO) rather than RP-1 and LOX.

Titans that carried Solid Rocket Boosters (SRBs) (Titan IIIC, IIID, 34D, and IV) had a second ISDS that consisted of several lanyards attached to the SRBs that would trigger and automatically destroy them if they prematurely separated from the core, said "destruction" consisting mainly of splitting the casings open to release the pressure inside and terminate thrust.

Titan III/IV SRBs were fixed nozzle and for roll control, a small tank of nitrogen tetroxide was mounted to each motor.

The second launch in October 1965 failed when the Transtage suffered an oxidizer leak and was unable to put its payload (several small satellites) into the correct orbit.

It was a US Air Force experimental communications satellite launched along with OV2-3, LES 3, and Oscar 4 from Cape Canaveral aboard a single Titan 3C rocket.

Around 80 seconds, the remainder of the shroud disintegrated, causing loss of launch vehicle control as well as the payload (a group of IDCSP satellites intended to provide radio communication for the US Army in Vietnam).

Designated the Titan 3A-1, this stage was powered by a twin nozzle Aerojet LR-87-AJ9 engine [4] that burned about 240,000 lb (110,000 kg) of Aerozine 50 and nitrogen tetroxide (NTO) and produced 1,941.7 kN (436,500 lbf) thrust over 147 seconds.