Italian Seppi looked as though he could be about to cause an upset when he won the opening set on a tie-break in the Spanish capital.
Both players struggled to force a break of serve in the next set, resulting in another breaker being required to determine a winner. On this occasion Ukraine's Dolgopolov was the victor, serving out 7-5 to set up a deciding set.
Seppi's chances of recording a win were hampered early in the third set as Dolgopolov claimed his service game at the first time of asking.
The world number 19 pressed home his advantage with a string of cross court winners to wrap up the match 6-7 7-6 6-3.