Twenty-year-old Margarita Gasparyan, a Russian making her Wimbledon debut, led 3-1 in the opening set but could not sustain the early onslaught as Williams ran out a 6-4 6-1 winner.
A fall by Williams in the sixth game, and a code violation warning for an audible obscenity, might have put off a lesser player, but the 33-year-old American put both behind her in claiming her 16th first-round win at Wimbledon in as many attempts.
She is targeting the feat of winning all four majors in the same year, last achieved in women’s singles by Steffi Graf in 1988.
Williams is also just a Wimbledon triumph away from the second non-calendar ‘Serena Slam’ of her illustrious career.
She has no enthusiasm to talk about the calendar grand slam, but knows her game has hit remarkable heights since losing in the third round at Wimbledon 12 months ago.
“I’ve had such an amazing year, I ended up winning the (US) Open, the (WTA) Championships, the Australian and France.
“I couldn’t have dreamt of a better 12 months so it’s been really great. I’m just excited about that and really focusing on that,” she said.
“I always focus on the moment. I don’t live too far in the future.”
Former semi-finalist Victoria Azarenka coasted through her opening match as she became the first woman to progress.
The 25-year-old Belarusian reached the last-four stage in 2011 and 2012, and overwhelmed Estonian Anett Kontaveit 6-2 6-1 in just 57 minutes on Court 12.
Serbian seventh seed Ana Ivanovic enjoyed a swift 6-1 6-1 victory over China’s Xu Yi-fan, and Australian Sam Stosur, seeded 22nd, won 6-4 6-4 against Montenegrin Danka Kovinic.
Johanna Konta’s wait for a first-round victory at Wimbledon continues after the British hope was overwhelmed by fourth seed Maria Sharapova.
Russia’s five-time grand slam winner dispatched Konta 6-2 6-2 to condemn Australia-born Konta to a fourth-successive defeat at SW19.
Konta reached the Eastbourne quarter-finals, losing to eventual champion Belinda Bencic, but was unable to make that momentum count yesterday.