Dolgopolov needed just 54 minutes to see off Ramirez Hidalgo 6-1 6-3, the Ukrainian taking advantage of three of his seven break points while not allowing his Spanish opponent a single break point in the match.
World number 25 Dolgopolov will now face 2002 winner Blake in the last eight, with the American defeating Swiss qualifier Marco Chiudinelli 6-2 6-4.
That victory improved Blake's record in 2012 to three wins in 11 matches having struggled with knee problems in recent years.
Also going through to the quarter-finals was fourth-seeded German Tommy Haas with a 6-4 7-5 triumph over Argentinian Leonardo Mayer.
Haas, who has now reached the Citi Open quarters five times in seven appearances, will next face compatriot Tobias Kamke, who also celebrated a straight-sets win in his second round clash as he downed Marinko Matosevic of Australia 6-4 6-3.
In the women's event, top seed Anastasia Pavlyuchenkova of Russia was taken to three sets before beating Hungarian Melinda Czink 6-2 2-6 6-3 in her second round match.
Fourth seed Vania King of America joined Pavlyuchenkova in the quarter-finals with a 6-2 7-6 (7/5) win over compatriot Irina Falconi, while another home player, seventh seed Coco Vandeweghe, was a 6-2 6-2 victor over France's Aravane Rezai.
King and Vandeweghe now face each other for a place in the semi-finals.
Not all the seeds progressed through though as number eight Olga Govortsova of Belarus suffered a surprise defeat at the hands of Eugenie Bouchard despite convincingly winning the first set and leading 3-0 in the decider, her 18-year-old Canadian opponent battling back both times to claim a 1-6 6-0 6-3 triumph.
Other second round winners were Slovakian duo Jana Cepelova and Magdalena Rybarikova.