Vizcaíno was born in Extremadura, Spain. He saw military service in the Spanish invasion of Portugal during 1580-1583. Coming to New Spain in 1583, he sailed as a merchant on the Manila galleon to the Philippines in 1586-1589.
In 1593 the disputed concession for pearl fishing on the western shores of the Gulf of California was transferred to Vizcaíno. He succeeded in sailing with three ships to La Paz, Baja California Sur in 1596. He gave this site (known to Hernán Cortés as Santa Cruz) its slightly misleading modern name "peace" and attempted to establish a settlement. However, problems of resupply, declining morale, and a fire soon forced its abandonment.
In 1601 the Spanish Viceroy in Mexico City, the Conde de Monterrey, appointed Vizcaíno general in charge of an expedition to locate safe harbours in Alta California for Spanish Galleons to use on their return voyage to Acapulco from Manila. He was also given the mandate to map in detail the California coastline that Juan Rodríguez Cabrillo had first reconnoitered 60 years earlier. He departed Acapulco with three ships on May 5 1602. His flagship was the San Diego and the other two ships were the San Tomas and the Tres Reyes. On November 10 1602, he entered and named San Diego Bay. Sailing up the coast, Vizcaino named most of the prominent features such as Carmel Valley, Monterey Bay, Sierra Point, Coyote Point (thus obliterating some of the names given these same features by Cabrillo in 1542).
One result of Vizcaíno's voyage was a flurry of enthusiasm for establishing a Spanish settlement at Monterey, but this was ultimately deferred for another 167 years.
Vizcaíno travelled from New Spain to Japan in 1611 as an ambassador, ostensibly to thank the Japanese government for its kind treatment to Rodrigo Vivero y Velasco, former governor of the Spanish Philippines who had been shipwrecked in Japan in 1609. He also returned Japanese men who had come to New Spain earlier with the embassy of Luis Sotelo. During his stay in Japan, Vizcaíno met with retired Shogun Tokugawa Ieyasu in Sumpu and acting Shogun Tokugawa Hidetada in Edo, as well as the powerful daimyo of Sendai, Date Masamune.
Vizcaíno then left the country to accomplish a mission to discover a fabled "Island of gold and silver" supposed to be in the sea East of Japan. His ship, the San Francisco, was crippled in bad weather, and he was forced to return to Uraga, his original point of departure. The following year, he left for New Spain on a boat the Tokugawa Bakufu had built for him, but he once again met with bad weather, and had to come back to Uraga.
Because of these two failures, it was decided that Date Masamune, would build a stronger ship for Vizcaíno in 1613. This ship became the San Juan Bautista, a 500-ton galleon which was used on the same occasion to dispatch a Japanese embassy to New Spain and then Europe, led by Hasekura Tsunenaga. It is said Sebastián Vizcaíno contributed his knowledge of ship technology and navigation skills to the building of the ship and the success of its mission.
Sebastián Vizcaíno wrote a report entitled "Account of the Search for the Gold and Silver Islands" in which he related his adventures in Japan.