Clay-court specialist Dominic Thiem and Tsitsipas are favoured more than Federer - who is in the same side of the draw as Nadal - by many bookmakers, while Alexander Zverev is considered to have a similar chance of success as the Swiss.
Federer reached the Madrid Open quarter-finals earlier in May in what was his first clay-court event in three years, but was forced out of the Italian Open quarterfinals with a leg injury.
While so much of the title speculation is focused on Rafael Nadal and Novak Djokovic - both play Monday - Federer enjoys the unusual-for-him position of lowered expectations. And they're still the dominant figures in men's tennis, responsible for the main story lines when the French Open starts Sunday.
Muguruza was unsettled by Townsend's mix of power and finesse in the opening set before she finally dictated the pace and found her range, hammering a series of forehand winners to gain the upper hand.
After making a bad start to the clay season by losing his openers at the Monte Carlo Masters and Barcelona respectively, the Frenchman's form appeared to be on the rise after making it all the way at the Bordeaux Challenger.
Tournament director Guy Forget put on a courageous face when asked about French hopes at Roland Garros this year. "I've been really putting in the hours in terms of keeping my cardio as much as I could with a knee injury, which is really impressive how I've been able to do it".
It is part of the 350-million-euro renovation of Roland Garros which has also seen Philippe Chatrier rebuilt in preparation for the addition of a roof from next year.
"I made a decision to meet with a psychologist and really open up about everything I have been feeling".
"I think now Simonne Mathieu is going to be my second option, because it's (a) cute court", she said after a 5-7, 6-2, 6-2 victory.
But one thing was never in doubt: fans are ready to see the legend play on the red clay. "You can feel good and then sometimes it can, you know, just pop up".
Canadian teenager Felix Auger-Aliassime also pulled out of the French Open because of an injury. "Just like Federer's reign isn't ending", said Riccardo Piatti, who coached Djokovic when the Serb was a teen and has worked with other top-10 players.
Slovak qualifier Kristina Kucova reached the second round of the French Open for the first time with a 6-4 6-2 win over former champion Svetlana Kuznetsova.