The three players, seeded first, third and fourth respectively, all progressed to the third round in straight sets, with world number one Nadal proving too strong for Teymuraz Gabashvili.
Going in search of a ninth title at Monte Carlo after being crowned champion eight years in a row between 2005 and 2012, Nadal swept the Russian aside 6-4 6-1 and he was later joined in the next round of the ATP Masters 1000 clay event by Wawrinka.
The 2014 Australian Open winner progressed with a 6-0 6-2 victory over Marin Cilic, while Federer, a three-time runner-up at the competition, defeated Radek Stepanek.
Federer took a wildcard to appear at the event for the first time since 2011 and ensured a happy return thanks to a 6-1 6-2 victory.
Canada's number eight seed Milos Raonic recovered from an early setback to see off Lu Yen-Hsun 6-7 (4-7) 6-2 6-1, while there were straight-set wins for Lukas Rosol and Fabio Fognini.
The duo saw off qualifier Michael Llodra and Spanish world number 45 Roberto Bautista Agut respectively.
Andreas Seppi, fresh from sending 13th seed Mikhail Youzhny out in the first round, progressed following a marathon 7-6 (7-5) 5-7 6-4 win over Pablo Andujar.
After almost two hours and 50 minutes on court, the Italian's reward is a meeting with Nadal.
Andujar's Spanish compatriot Tommy Robredo recovered from a poor first set to progress, beating Julien Benneteau 4-6 6-0 6-1 to book a clash with Raonic.
Grigor Dimitrov is safely through after coming from a set down against Albert Ramos, while Nicolas Almagro enjoyed an easier time of it as he ended Nicolas Mahut's campaign.
Guillermo Garcia-Lopez and Pablo Carreno Busta rounded off the day's play as they racked up straight-set wins over Alexandr Dolgopolov and Gael Monfils respectively.
World number 38 Garcia-Lopez was a 6-1 7-5 victor and Carreno Busta now looks ahead to a daunting third-round clash with second seed Novak Djokovic.