The comfortable victory on a sweltering night at the Estadio Romano in Merida meant Vicente del Bosque's side qualified as group winners with two matches to spare and eight wins out of eight.
"It was a good day and even if we perhaps weren't at our best it was enough to secure qualification," Del Bosque said at a news conference.
David Villa fired narrowly over from Xavi's pass in the 24th minute and Fernando Torres did the same a minute later after a swift break.
Substitute Santi Cazorla made it 2-0 when he crashed the ball in from close range in the 82nd minute and Juan Mata came off the bench to round off the scoring in added time with a cool finish from Cazorla's cross-field pass.
Their were wild celebrations at the final whistle and cries of "Espana! Espana!" rang out around the arena.
"We tried to do what we could but Spain were a lot better and that's the reality," Estonia coach Tarmo Ruutli said.
"It will be a different story of course in South Africa. There will be a lot of strong teams wanting to win and the World Cup is always a little bit about luck."
Bosnia's 1-1 draw with visiting Turkey in their Group Five clash on Wednesday had set Spain up for qualification and the win followed Saturday's 5-0 thrashing of Belgium.
