Commissioned at the end of World War II, Sirago conducted her shakedown cruise off the East Coast and in the Caribbean Sea during the fall of 1945.

On returning to New London, Sirago commenced duties that included training services for the Submarine School and for the fleet's destroyer force; experimental exercises to evaluate new techniques and equipment; type training; and fleet exercises that took her from Davis Strait into the Caribbean.

In December 1948, she entered the Philadelphia Naval Shipyard for a Greater Underwater Propulsive Power Program (GUPPY) conversion; and, on 25 July 1949, she left the yard for Norfolk, Virginia, where, as a modernized high-speed attack submarine, she joined SubRon 6.

Secondary missions included antishipping warfare, intelligence gathering, and the provision of services for research and development studies.

That fall, she deployed to the Middle East for CENTO exercise "MIDLINK VI"; but, during the remainder of the 1960s and into the 1970s, her operations were similar to those of the 1950s.