The favourites powered ahead in the first quarter before Spain recovered to within a point at the interval.
But Spain could not contain the Americans’ powerful attack and LeBron James and Kevin Durant scored crucial baskets in the final period.
Durant led USA’s offence with 30 points, while Spain’s Pau Gasol scored 24 at London’s North Greenwich Arena.
Spain applied pressure to the USA defence for long periods to keep in touch but with their wealth of experienced NBA players the Americans ultimately had too much strength in depth.
The United States had scored over 100 points in five of their seven matches leading to the final, including a record 158 against Nigeria, and they continued their imperious form as they strode to a 35-27 lead by the end of the first quarter.
Juan-Carlos Navarro caught USA on the break to reduce the lead to four with two minutes left to half-time and with three seconds of the half remaining, Andre Iguodala gave away a pair of free throws for an unsportsmanlike foul to enable Spain to go in at the interval just 59-58 down.
As 13,000 supporters looked on, including American actor Arnold Schwarzenegger and Mayor of London Boris Johnson, the USA began to relax and a much-needed three points from Durant put them six points up at 93-86 with 06:25 on the clock.
Another crucial three from James, on his way to 19 on the night, made it a nine-point game with under two minutes left to play and despite a Marc Gasol basket in the closing seconds the Americans ultimately won with a degree of comfort.
Kobe Bryant said: “It was a good journey for us. It was just tough. So to be standing here at the moment having played a tough opponent in Spain, with another gold medal, it’s a huge accomplishment.
“We have a lot of talented players coming up. Hopefully we will continue to build our programme, continue to mentor the young fellas coming up, the college ranks and the young fellas in the pro ranks and continue to carry on the tradition.”