The 22-year-old Russian became the first unseeded women's champion at Eastbourne since American Chanda Rubin in 2002, and is the first qualifier to win the title.
"Actually, I cannot believe it that I win the title," Makarova said. "I'm thinking that I have to play one more match. I cannot feel like it's finished, it's done."
Azarenka struggled from the start and appeared to be carrying an injury, but refused to reveal what it was.
"It's my problem, I'll keep it to myself," Azarenka said. "I still have to treat it and I don't want to put it out there. It's not a big thing."
The hobbled 20-year old from Belarus sank to her knees after Makarova hit a winning return to break for 2-0. While Azarenka was moving gingerly at times, she competed throughout, holding a break point at 2-0 and another at 4-2 before forcing a backhand error to break in the ninth game as Makarova failed to serve out the set.
Makarova also faced two break points at 5-5 before taking the tiebreaker.
Leading 2-1 in the second set, Azarenka called for her coach and appeared close to tears. She went on to concede her serve at 2-2 when she made a forehand error.
Makarova, who saved 10 of 11 break points in the match, fought off four break points to hold for 4-2 and two more at 4-3 before claiming victory.
Makarova is the first qualifier to win a title since Alexandra Dulgheru in Warsaw last year.
In the men's final, Llodra saw off Garcia-Lopez 7-5, 6-2.
The eighth-seeded Llodra gave up just two points on serve in the opening set before hitting a winning backhand to break Garcia-Lopez in the final game.
In the second set, fifth-seeded Garcia- Lopez double-faulted to gift Llodra a break for 4-2, and the Frenchman broke again in the final game, claiming victory on his fourth match point.
It was Llodra's second tournament victory of the year after his win in Marseille, and the fifth of his career.