After a sloppy start that saw Spain lead much of the opening quarter, the U.S. finally settled into their familiar rhythm, turning a 10-0 run into a 17-point halftime lead.
From then on there was no way back for Spain as the U.S. extended their Olympic winning streak to a staggering 49-0.
Only two other teams can claim such a run of domination in an Olympic team sport.
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The U.S. men's basketball team earned seven consecutive gold medals from 1936-1968 while India claimed six-straight men's field hockey titles from 1928-1956.
"It's mind boggling when you think about it what this team has been able to accomplish, this programme," said U.S. coach Geno Auriemma. "There is such a level of expectation, such a level of respect and it filters down. Everyone who puts that jersey on they get it. We're doing stuff that may never be done again."
For Spain, the silver was their first medal in Olympic women's basketball.
Earlier, Serbia beat France 70-63 in the bronze medal game.
FOUR GOLDS
With the U.S. victory Sue Bird, Tamika Catchings and Diana Taurasi joined former team mates Teresa Edwards and Lisa Leslie as the only players to win four gold medals in basketball.
Taurasi and Lindsay Whalen paced the U.S. on the scoreboard, pouring in 17 points apiece, while Maya Moore potted 14.
"It's pretty incredible," said 34-year-old Taurasi, who left the door open for a possible fifth Olympic run. "We had the goal to win the gold medal but there is something more to it than that. It's not about one person, one coach, it's about how can we make this the best basketball team ever."
Team USA captain Bird, who sat out the semi-finals with a knee injury, was back in the lineup and was also non-committal about her national team future while Catchings confirmed Saturday's gold medal game was her last.
Humbled 103-63 by the U.S. in preliminary round play, Spain had looked determined to offer more resistance in the final, holding a 17-14 lead late in the opening quarter.
But after Angel McCoughtry hit a layup and connected on two free throw attempts the U.S. never trailed again.
"It's one thing to do the unexpected, it's another to do what you are expected to do year-after-year, game-after-game, quarter-after-quarter," said Maya Moore.
"This team didn't get complacent. I think that is the sign of a true champion, someone who loves the game."
(Additional reporting Mary Milliken; Editing by Nina Chestney and Ken Ferris)
