It was her sixth career title and first since Quebec City in 2013 as well as her first at the Premier-level.
The Czech snapped Azarenka's 14-match winning streak in Doha and also foiled the Belarusian's attempt to clinch a record third Qatar Open title.
"It's an amazing feeling. I'm really excited and I've been working towards this for a long time. I'm happy at the way season has progressed," said Safarova, who along with Bethanie Mattek-Sands had won their first grand slam doubles titles at the Australian Open last month.
Contesting their first final of the season, Safarova broke Azarenka in the very first game and asserted her supremacy gradually. Though Azarenka broke back in the sixth game, Safarova returned the compliment again in the ninth and held her serve in the next to take the first set.
The plot was no different in the second set in which Safarova broke Azarenka twice-in the third and the ninth games, firing seven aces in the match including three-in-a-row to seal the contest.
Having lost all her six previous encounters to Azarenka, the Wimbledon semifinalist Safarova, raised her game to a new level at the Khalifa Tennis Complex in the match which lasted one hour and twenty seven minutes.
"I mean, it's up there. Obviously semifinals at Wimbledon was a very high achievement for me as well. It's the first premier WTA win of a tournament, so I'm really excited. I think it's like I'm playing more consistent.
"My game improved a lot throughout the last couple of years. It took me quite a few years to get to this point. I hope it's not a finish point and I can still improve that," added Safarova, who will move four places up to 11 when the latest WTA rankings are released on Monday.
For Azarenka, who was playing her first final since the 2014 Brisbane, where she lost to Serena Williams, it was more heartbreak, in a match in which she committed 21 unforced errors.
"There's been a lot of progress this week, a lot of good things happened, a lot of great matches. I was looking as many matches in a row to try to get used to that. And I had a lot of great things actually this week that I can take and still keep working. I'm still really motivated," said Azarenka.