Serena defeats Azarenka for Italian Open title
The top-ranked American will enter the French Open, which starts next Sunday, on a career-best 24-match winning streak.
Williams was coming off consecutive titles in Miami; Charleston, South Carolina; and Madrid last week.
She didn't drop a set while winning this title.
Williams' only previous title at this clay-court event came in 2002, when she beat Justine Henin in the final.
That was also the year she won her only title at Roland Garros. Last year in Paris, Williams lost in the opening round of a major for the first time, falling to 111th-ranked Virginie Razzano of France.
Later, Roger Federer and Rafael Nadal were renewing their rivalry in the men's final at the Foro Italico.
On a pleasant spring day, Williams immediately took control by breaking Azarenka's serve twice to take a 3-0 lead in the opening set.
The 15-time Grand Slam winner slugged winners at will off both Azarenka's first and second serves, stepping into the court to dictate play at every opportunity.
Azarenka grew distraught at the end of the first set, twice slamming her racket on the court in desperation.
After trading breaks midway through the second set, Williams took control again when Azarenka double faulted to hand her a 5-3 lead. Williams then served out the match at love and let out a big scream when she unleashed a backhand winner down the line to close it out.
Williams held a massive 41-12 edge in winners and served nine aces to Azarenka's none.
Williams improved to 12-2 in her career against Azarenka, who spent 51 weeks at No. 1 before Williams reclaimed the top spot in February.
Williams had twice won 21 matches in a row before, although both of those runs came more than a decade ago, in 2002 and the beginning of 2003.
Martina Navratilova established the longest women's winning run in the Open Era at 74 matches in 1984.
At 31, Williams is back at the top of her game after missing 11 months in 2010 and 2011 with a right foot injury and a pulmonary embolism.
It was Azarenka's first final since beating Williams for the title in February at Doha, Qatar. That followed the Belarussian's Australian Open victory. Since then, Azarenka has been slowed by right ankle and left foot injuries.
It was the 51st title of Williams' career. Navratilova also holds the record in that category with a seemingly insurmountable 167 titles. Williams moved within two titles of matching Monica Seles for ninth on the all-time list.
Williams was already first among active players and now has seven more titles than her sister Venus, who is second on the list and watched the final from the stands.
Earlier in the women's doubles final, Su-Wei Hsieh of Taiwan and Peng Shuai of China upset the top-ranked Italian pair of Sara Errani and Roberta Vinci 4-6, 6-3, 10-8.