Most of those responding to this idea are tending to put 2009 Preakness Stakes winner Rachel Alexandra among the great fillies of the past 100 years.
There is plenty of evidence to support that. Racing against colts puts the bar high, and racing for the classics is placing the standard very high.
Therefore, I would also nominate a pair of old-time stars, Kentucky Derby winner Regret and Preakness winner Nellie Morse.
Regret (1912 – April 11, 1934 by Broomstick x Jersey Lightning, by Hamburg) won the 1914 Hopeful, 1915 Kentucky Derby.
Nellie Morse (1921 – 1941 by Luke McLuke x La Venganza, by Abercorn) won the 1924 Preakness.