More than 700 sailors and officers from the two countries are taking part in the effort to further improve military-to-military relations and benefit from each other's experience, Lt. Commander Salman Ali said.
He gave no other details, and only said they would issue a statement about the exercises later Tuesday.
The navies will be focusing on "undersea" and "explosive" warfare and deep water exercises, Capt. Hank Miranda, commander of the US Destroyer Squadron 50, told reporters Monday in southern port city of Karachi.
"These (exercises) are not directly related to checking the movement of terrorists. The purpose is to practice skills such as communications and try to keep the sea trouble-free
Pakistan is a key ally of Washington in its war on terror, and the exercises, called Inspired Siren, came two months after Pakistani and US troops participated in a joint counterterrorism exercise in northwestern Pakistan.
It is the first time that in the past seven years that US Navy ships have come to Pakistan's main port on its southern coast. Two Pakistani destroyers, PNS Tariq and PNS Shahjahan, as well as submarines and helicopters will join the exercise, which ends June 28.
Karachi, the capital of southern Sindh province, has been the scene of several acts of terrorism in recent years.