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Having already beaten ex-world number one Ana Ivanovic and seventh-seed Mario Bartoli on the way to the quarter-finals, Barthel put up another battling performance to take Friday's game to three sets despite losing the first.
This was Azarenka's fourth win over the 21-year-old German this year, but the world's top player needed nearly three hours to see off the German wildcard at the clay-court tournament.
"She keeps producing some great tennis and she showed again today why she is a tough one to beat," said Azarenka after Barthel blasted down 13 aces compared to her five.
"Her serve is definitely up there with the best, after more than two-and-a-half hours she was still blasting down aces.
"I have been saying for a while she is one to watch."
In the semi-finals, Azarenka faces Poland's Agnieszka Radwanska who earlier beat French Open champion Li Na of China in her quarter-final.
Li went down 3-6, 6-2, 6-3 to the Polish fourth-seed, despite dominating the first set.
The Chinese struggled to cope as Radwanska raised her game with a series of drop shots and strong returns in the second before carrying her improved form into the third.
"I was more aggressive in the first set, but things turned after I broke her serve in the second," said 30-year-old eighth-seed Li.
"I didn't get many first serves in after that and it left me pretty down, I was really pissed off at myself walking off court.
"At least, I know I can still slide out there, I haven't played badly in my three games this week, so at least I know I can continue on the right path."
With Roland Garros to start on May 27, Radwanska said she was enjoying finding her feet on clay courts as she bids to win her first Grand Slam title having claimed nine wins on the WTA tour.
"I am enjoying my tennis and just trying everything at the moment, which probably worked against me in the first set" said the 23-year-old, ranked fourth in the world and who claimed her ninth tour win at Miami recently.
"I was more calm in the second set and I am just happy I could turn things around. I just hope this is my year, so I can take the next step."
All of Radwanska's four losses this year have come at the hands of Azarenka and having also reached the semi-finals here last year, the Polish number one said it takes a special effort to beat the world number one.
"You have to be at the top of your game and play some great tennis to beat her," admitted Radwanska.
In Friday's other last four ties, world number two Maria Sharapova takes on fifth-seed and US Open winner Samantha Stosur while Wimbledon champion Petra Kvitova faces Germany's Angelique Kerber.
Results from the fourth day of the WTA tournament on Friday (x denotes seeding):
Quarter-finals
Agnieszka Radwanska (POL x4) bt Li Na (CHN x8) 3-6, 6-2, 6-3
Victoria Azarenka (BLR x1) bt Mona Barthel (GER) 6-4, 6-7 (3/7), 7-5
