The Azzurri had been unbeaten in qualifiers since losing 3-1 to France in a European Championship qualifier in 2006, but Ventura's decision to play a 4-2-4 formation against Spain at the Santiago Bernabeu appeared to backfire.
The home side were 2-0 up at half-time thanks to a brace from Isco, and substitute Alvaro Morata added a third in the 77th minute to ensure Spain's record of never losing a World Cup qualifier at home remained intact.
Ventura told Rai Sport: "In general, there was a difference in fitness levels and quality.
"We gifted them some situations and helped them out. We went 2-0 down with the first two shots on target, even though we had the best chances from open play and David de Gea made key saves.
"Right now we are human and Spain are less human."
The result leaves Italy second in Group G, three points adrift of Spain, and Ventura promised his side would learn from the defeat as they go into Tuesday's game against Israel at Sassuolo's Mapei Stadium.
"We are carrying on a project and one game cannot change that," said Ventura. "The basic problem is what we are and what we want to become. This was an experience, we'll analyse what we can learn from it and how we can develop.
"If one match hits our self-confidence, it means we are not competitive, so I cannot believe that."
Striker Lorenzo Insigne claimed his team-mates are confident the defeat will not rule Italy out of the World Cup in Russia, telling Rai Sport: "These games help you grow.
"We knew that it was difficult against a great side, but now we will analyse the errors we all made and, along with the coach, will try to fix the situation.
"We realise that to reach the World Cup we must make a sacrifice, but if we stay united and work hard, we can achieve our objective."