Kirdyapkin finished Saturday's race 54 seconds ahead of Jared Tallent of Australia, who took silver. Si Tianfeng of China was 1 minute, 17 seconds behind to win bronze in the event along the streets of central London.
Kirdyapkin took a commanding lead at the 45-kilometre mark and crossed the finish line near Buckingham Palace in 3 hours, 35 minutes, 59 seconds. He broke the Olympic record of 3:37:09 by 1 minute, 10 seconds. The mark was set by Alex Schwazer of Italy at the Beijing Games four years ago.
Schwazer had failed a doping test conducted by the World Anti-Doping Agency before arriving in London and was excluded from the Olympics. The 27-year-old athlete, who admitted to using the blood-boosting hormone EPO, was removed from the Italian team Monday. He said he felt immense pressure to defend his title in London.
Kirdyapkin won the world championships in 2005 and 2009. He failed to finish at the 2008 Beijing Games.
"Compared with Beijing, today it all went perfectly well," Kirdyapkin said. "It's the Olympic gold medal, so for me it's the most important."
His wife, Anisya Kirdyapkina, was competing in the 20K race on Saturday. She finished 1 minute, 25 seconds behind the winner and Russian teammate Yelena Lashmanova.
Kirdyapkina was a medal favourite at the Olympics. She won bronze at the worlds in South Korea and finished second at the 2010 European championships.
Russia last won the 50K walk at the 1992 Barcelona Games. With Schwazer out, the Russian walkers were the favourites to claim the gold.
World champion Sergei Bakulin, who was one of the medal favourites at the Olympics and led most of the race, finished sixth. Bakulin won gold at the world championships in Daegu, South Korea, last year.
His Russian teammate and a medal favourite, Igor Erokhin was fifth.
Tallent's wife, Claire, was also competing in the 20K race on Saturday. The couple's hopes to reach the podium at the Olympics on the same day were dashed after she was disqualified on a technical violation.
Competitors in the walk can be disqualified if both their feet appear to be off the ground at the same time.
"I am so upset," she said. "I was in the best shape of my life. I was giving all I had, I was doing my personal best. It was just a lapse of concentration. All the constant training, day after day, morning after morning. I worked so hard for this," she said.
The sadness over her own failure was trumped by the joy she felt for her husband.
"I am so proud," she said. "I don't want to take anything away from Jared today. Today it is his day."
Jared Tallent won silver in Beijing and took bronze at the worlds in South Korea last year.
He drew valuable lessons from the race at the worlds to clock his personal best of 3 hours, 36 minutes, 53 seconds Saturday.
AP Sports writer John Pye contributed to this report.