Arsenal's Beth Mead finished off a smart team move to give Phil Neville's Lionesses the half-time lead, with Ellen White firing home just seconds after the restart.
Spain pulled one back through substitute Aitana Bonmati but England played out the remainder of the contest, in Swindon, to seal the win.
Neville, true to his word ahead of the friendly double-header, made plenty of alterations from Friday's 1-0 defeat to Canada as only Rachel Daly and Toni Duggan retained their places.
England, who sit 10 places above their 13th-ranked opposition, faced early pressure from Spain but the home side settled and opened the scoring when Mead slid in at the back post to convert White's cross.
England needed less than a minute of the second half to double their advantage, White finishing brilliantly from Jill Scott's pass to put the hosts in control.
Spain reduced the arrears at the midway point of the second half as substitute Bonmati tucked home.
“We made that many changes in the second half that we lost our rhythm, but I made those changes because I wanted us to see out a game,” said England head coach Neville.
“If you get to a quarter-final or semi-final, you're not going to win games easily. I wanted to see how we were going to cope. I was disappointed a little bit with our composure. I've rotated and given everyone a chance and now it's time to get into World Cup mode.”
Neville has two further warm-up matches, against Denmark and New Zealand, before England's World Cup gets under way with a June 9 clash against Scotland.