The 30-year-old former number one, seeded ninth at the premier clay event in the Spanish capital, made the most of Azarenka's nervous start on the blue dirt of the Manolo Santana show court to race into a 4-0 lead.
With the sliding roof of the futuristic Magic Box arena open to the baking Madrid sun, Williams made the most of Azarenka's error-strewn start on the blue dirt of the Manolo Santana show court to race into a 4-0 lead.
After breaking the Belarussian's serve for a third time to clinch the first set, Williams turned the screw with another break early in the second and clinched victory on her first match point when Azarenka, also runner-up last year, completely missed an attempted return.
It was the American's second title of the year after her success on the clay at Charleston last month and her 41st singles crown overall, putting her in joint 13th on the all-time list with Belgian Kim Clijsters.
"My whole thing is just to play consistent and that is what I have been doing the past couple of weeks," Williams told a news conference.
"I belong on a tennis court and that's where I feel amazing," she added.
A 13-times Grand Slam singles champion who was last number one in October 2010, Williams is projected to rise to number six when the rankings are updated and said she had her eye on extending her overall tally of 123 weeks at the top.
"I don't play to be number two, I don't think Victoria plays to be number two," she said. "We all play to be the best."
Serena beat her sister Venus in the French Open final in her sole triumph at Roland Garros in 2002 but has not been past the quarter-finals since 2004, leading to a perception she is less comfortable on the dirt than grass or hardcourt.
"It's a big myth because I actually love the clay, I grew up on clay," Williams said.
"My results haven't been stellar but I have won the French Open, the ultimate claycourt tournament," she added. "Actually I like it more than the grass which is weird."
It was only Azarenka's third defeat in a year in which the 22-year-old won her first grand slam singles title at the Australian Open, which lifted her to the top of the rankings, and has earned more than $4 million in prize money.
Williams clubbed 26 winners to Azarenka's six and smashed down 14 aces, while her opponent did not manage a single one and offered up six double faults.
"She was just so much better than me today," Azarenka said.
"I do need to return a bit better and definitely improve my serve which today was just a disaster.
"These kinds of matches make you realize you have to take a moment and look at what you can do better."