Top seed Williams was forced to play some of her best tennis by resolute Kerber in an engrossing Centre Court duel in which her formidable firepower proved decisive in a 7-5 6-3 over her German opponent.
Kerber had stopped Williams in the Australian Open final to win her first grand slam title and last month Spain's Garbine Muguruza also kept the 34-year-old waiting to equal Graf's mark when she beat her in the French Open final.
Williams, who racked up grand slam number 21 against Muguruza at last year's Wimbledon, also stumbled at the 2015 U.S. Open, losing to Roberta Vinci in the semi-finals when a calendar year Grand Slam and Graf's record loomed.
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But this time Williams would not be denied.
To her great credit fourth seed Kerber used her skilful shot placement and scrambling ability to stay in contention throughout a fascinating match of contrasting styles.
But with the Williams serve at its destructive best there was only so much punishment the 28-year-old Kerber could absorb on a breezy Centre Court.
The end came quickly when the German was broken for the second time in the match in the seventh game of the second set and Williams roared to the title with a love game, sealing victory with a simple volley before collapsing to the turf.
SWEET VICTORY
"It's been incredibly difficult not to think about it (Graf's record)," a smiling Williams, cheered on by celebrity couple Beyonce and Jay Z as well as sister Venus in her support box, said on court as she clutched the Venus Rosewater Dish.
"I had a couple of tries this year but lost to two great opponents, one of them being Angelique. But it makes the victory even sweeter to know how hard I worked for it.
"Thanks you guys for being out here to see number 22, this is awesome," she said to an appreciative crowd who were treated to a one hour 21 minute final full of absorbing rallies.
Kerber warmly embraced Williams once the emotional American rose to her feet -- saying later she had been beaten by a "great champion and a great person.
"Serena was serving unbelievable today. She really played an unbelievable match," Kerber who will rise to second in the WTA rankings on Monday, said.
"I think I didn't lose the match, I think she won it."
Williams won 38 of 43 points on her first serve and faced only one break point, at 3-3 in the second set, which she saved with one of the 13 aces she delivered.
"It's the single greatest weapon in the history of the women's game, followed closely by her will to win," was three-times men's champion John McEnroe's succinct summing up of what puts world number one Williams in a league of her own.
INTENSE SCRAP
Kerber reached the final without conceding a set and scuppered hopes of a first all-Williams grand slam final since 2009 when beating Venus in the semis.
With a stunning win against Serena in Melbourne, the German walked on court full of belief -- winning the opening point with a cleanly struck forehand.
Williams, patrolling her baseline with menace, bit into the Kerber serve in the second game but failed to convert any of the three break points she had.
An intense scrap developed from then on as Williams attacked incessantly and Kerber bravely traded blows.
Williams bent double and pumped both fists when winning a long rally on serve at 3-3 as Kerber briefly threatened.
She was also taken to deuce on serve at 4-4 and 30-30 at 5-5, yelling "C'mon!!" as she kept her nose in front.
Having coped with the heavy artillery heading her way, Kerber's downfall was self-inflicted as two poor errors opened the door for Williams to take the opener.
Kerber then screamed her delight at one searing winner early in the second set and finally earned a break point at 3-3 -- Williams responding with consecutive aces.
Williams ended up in a heap on the floor in the next game after a close-quarters exchange, but got up to break for a 5-3 lead as Kerber finally crumbled.
She joyfully returned to the turf shortly afterwards as her trusty serve powered her home.
Serena returned to Centre Court later to claim a sixth Wimbledon women's doubles title with Venus against fifth seeds Timea Babos and Yaroslava Shvedova.
All in all, not a bad day's work.
(Reporting by Martyn Herman; editing by Ken Ferris)
