Williams reached 19 with her Australian Open triumph last month and despite being 33 years old, there is little sign that her powers are waning.
Agassi, who won eight majors before retiring and settling down with Germany's Graf to raise a family, said his wife does not fret over the breakfast table about losing her record.
"She was thrilled with her career, she had no regrets, she did everything she could do and that's all she ever cared about," Agassi told Reuters TV at the launch of the BILT by Agassi & Reyes range of gym machines near London.
"But what Serena is doing is remarkable.
"She's arguably the greatest ever, it would be easy to argue that regardless of 22 or not.
"Records are meant to be broken and if Serena does it would be a beautiful thing to watch."
Williams is currently third on the all time list, behind Australian Margaret Court's total of 24 and Graf's professional era haul of 22.
Agassi knows what it feels like to watch some of his benchmarks being scrubbed out.
"I just found out my four Australian Opens was broken by (Novak) Djokovic," he laughed. "But I was just thrilled to watch a good match. It's great for the game."
(Reporting by Martyn Herman, editing by Pritha Sarkar)
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