The Roma midfielder slotted home from the penalty spot to level the scores in the 82nd minute after Vitolo had put the visitors in ahead in Turin.
De Rossi's equaliser against Spain means he is now the Azzurri's top scorer among active players. The goal takes his personal tally for the national side to 19, putting him level with Roberto Bettega in the all-time list.
Alessandro Florenzi also put in a solid performance as he started and ended the game at Juventus Stadium.
The Giallorossi pair formed two fifths of the Azzurri midfield alongside Riccardo Montolivo, Marco Parolo and Mattia De Sciglio
The 1-1 draw extends Italy's unbeaten run in qualifiers to 52 games and sees them move up to four points in Group G, level with Spain and two points behind Albania.
After the match De Rossi spoke enthusiastically about Italy's second-half display.
"We played much better in the second half than in the first," De Rossi said. "We played with heart – that's what Italy are about.
"With a tad more luck there at the end we might even have come away with all three points...”
Florenzi meanwhile took to Instagram to express his delight with the team's ability to claw back a point. He posted a photo of a grinning De Rossi in the changing room and wrote: “Well done, lads. Great fightback. Forza Azzurri!”
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