Tsitsipas was left broken-hearted after a five-sets defeat by Novak Djokovic (36) in the 2021 Roland Garros final before another loss to the Serbian at January's Australian Open, but the Greek has barely put a foot wrong in Paris this year.
Tsitsipas, who has only dropped one set in his four matches, will face his biggest test when he meets world number one Carlos Alcaraz in the last eight.
The fifth seed continued his charge by battling back from an early break to wrap up the first set and surged through the next, as Ofner's hopes of being the first qualifier to make the quarter-finals of the claycourt major since Marcelo Filippini in 1999 faded fast.
The Court Suzanne Lenglen crowd began a Mexican wave in the third set and Ofner soon found himself trailing 5-0 as the world number 118 struggled to deal with the Tsitsipas tsunami.
He was finally put out of his misery by the Greek who closed out the victory on serve.
