The race is part ultra-marathon, part tribute to those who died trying to cross the Wall, which the East German communist regime hastily erected in 1961 and stood for 28 years.
Precious little of the original concrete structure remains, most of it hurriedly torn down when East Germany collapsed in late 1989.
The longest single section is the kilometer-long East Side Gallery, where the former symbol of oppression is now covered in art, a popular backdrop for tourists posing for selfies.
What was once a heavily-fortified border strip that encircled West Berlin and patrolled by guards under shoot-to-kill orders, was in 2006 turned into the 'Mauerweg' or Berlin Wall path.
It passes iconic landmarks such as the Brandenburg Gate and Checkpoint Charlie as well as leafy suburbs, farmland and forests.
Along the route, memorials tell the personal stories of many of the around 130 people killed along the Wall.
"When you move around Berlin now, you hardly see any of the Wall left, but when you run the path and see its scale, you have a better understanding of the divide it caused," said race organiser Olaf Ilk, who was born in East Germany and was 24 when the Wall fell.
- Mental challenge -
The mammoth race is not for the faint-hearted: it is effectively four marathons back-to-back.
"You know you are going to feel pain, you have to accept it and think 'I can do one step more," said Patrik Gullerstrom, from Stockholm, who hopes to finish in under 17 hours and has run the race four times previously.
The course record, set by Briton Mark Perkins in 2014, stands at a mind-blowing 13 hours, 6 minutes for the 100 miles.
Russian-born Israeli Tom Shenbrun, 50, whose grandfather was part of the Red Army army which invaded Berlin in 1945, was inspired to run the race by the Wall's history
"As a Jew, it's something very special. You feel the history all along the course, you see the guard towers and you can understand how it divided a nation, families, friends," he said.
The East German authorities "were prepared to shoot people on the basis of ideology. History is something we must learn from and must not be repeated," he added.
The Wall's history is entwined in the race's DNA.
Registration for the following year's race always opens at 18:57 (1657 GMT) on November 9 -- marking the exact moment in 1989 when East Germany lifted its travel ban, triggering the Wall's demise.
Each year, one Wall victim features on start numbers and finisher medals, while a ceremony is held at the spot where they died.
For the first race in 2011, Chris Gueffroy, the last person shot dead on the Berlin Wall, was honoured.
He was killed in February 1989, nine months before the Wall fell, and on Sunday, Gueffroy's mother Karin will present medals at the finishers' ceremony.
- Political prisoners -
Last year, the Wall's youngest victim, Joerg Hartmann, a 10-year-old boy shot dead by East German border guards in 1966 while trying to visit his father in the west, was honored.
Having each been asked to carry a gift for him, last year's runners piled cuddly toys at the spot where he was killed.
"I still get goosebumps thinking about it," admits Ilk.
For the organizers and 400 helpers, all volunteers, a sleepless night is par for the course.
Logistics co-ordinator Andreas Pfeiffer must ensure half a tonne of provisions reach each of the 26 stations along the route.
He first got involved because of his personal Cold War story.
Raised in East Germany, Pfeiffer spent two years in prison up until 1984 after being arrested trying to flee across the Iron Curtain at the Hungary-Austria border.
He was freed to West Germany -- one of 33,755 political prisoners released for 3.5 billion Deutschmarks by East Germany under a scheme between 1963 and 1989, according to government figures.
"I was never a runner, but when I first heard about the race, I had to get involved," he said.
"I still get goosebumps every time I cross the old border between East and West Germany -- that'll never go away."
GETTY IMAGES NORTH AMERICA/AFP / Alberto E. Rodriguez 
AFP / LOIC VENANCE 
AFP / FADEL SENNA 
AFP / STR