He had his first career defeat in his second bout, when he faced Enrico Bertola on August 12 of that year, in Rome, dropping a ten-round decision.

As soon as his fourth fight, Spagnolo challenged for the Italian Heavyweight title, winning it with a twelve-round decision over Giovanni Martin, in San Remo.

Spagnolo then abdicated the championship in order to move to the United States, where more famous opponents and the possibility of a world title shot awaited.

He scored his only three career knockout wins during this streak, beating Mike Fisher in five, Louis Clark in three and Jim Lake in five.

This pattern of beating almost completely unknown fighters would continue on for the rest of his career, but he managed to also fight with Roland La Starza (who later challenged Marciano for the World Heavyweight title), losing by a ten-round unanimous decision on November 16, 1950, in Brooklyn, New York, Coley Wallace, losing to him by a ten-round decision on December 11 of the same year in Washington, D.C., and Nick Barone (who later challenged Charles for the World Heavyweight title), losing to him by a ten-round unanimous decision on March 15, 1951, in Syracuse, New York.