After losing the opening set 7-5 on a tiebreak, Spadea trailed 3-5 on the Russian's serve in the second before clawing his way back into the match in searing heat at the Los Angeles Tennis Center.
The Florida-based professional, who clinched his only ATP title in Scottsdale in 2004, took advantage of two double-faults by Tursunov to break his opponent before winning the next three games to level the match at one-set all.
Riding a wave of momentum, Spadea broke again in the fifth and ninth games of the final set to seal victory in two hours and 20 minutes.
Before the two players exited the stadium court, Spadea was presented with a cake by an ATP official and the crowd cheered the American by singing "Happy Birthday."
"That was a great mental match for me," Spadea told reporters. "I've been working on my game a lot this year and sometimes you forget to just hang in there and compete hard. It was a great win for me."
Asked to assess his comeback from 3-5 down in the second set, he replied: "I can do all things, man, if I believe it -- and if somebody double-faults at the right time."
Spadea will meet compatriot James Blake in the quarter-finals after the second seed beat Paul Goldstein 6-0 1-6 7-5 in the last match on the stadium court.
RACED THROUGH
Blake, hunting his first ATP tournament success in six months, raced through the opening set in under half an hour before Goldstein followed suit in the second.
After Blake saved a match point at 30-40 in the 10th game of the final set, he immediately broke his opponent before firing down three successive aces to secure the win.
Czech Radek Stepanek, out of action for six months last year because of a neck injury, ousted sixth-seeded wildcard Mardy Fish of the U.S. 6-2 6-2.
Stepanek, who reached his first semi-final of the season in Gstaad last week, broke Fish twice in each set to breeze through in just over an hour.
The Czech will meet little-known American Zach Fleishman in the last eight.
Local favourite Fleishman, who stunned top-seeded Fernando Gonzalez of Chile in the previous round, continued his dream run with a 7-6 6-3 victory over fellow American Robert Kendrick to reach his first ATP quarter-final.
The 27-year-old, a former student on the UCLA campus hosting this week's event, edged the first set 7-4 in a tiebreak before breaking his big-serving opponent in the first and ninth games of the second.