Eleventh seed Gilles Simon bowed out of the Monte Carlo Masters on the first day as he was beaten in straight sets.
Simon was broken by the Spaniard early on and would not recover, losing the opener 6-3, before a second-set break put Bautista-Agut ahead in the second.
Simon would level, and then the players traded breaks, before the world number 52 took the tie-break to six.
Simon was not the only seed to go out, with Fabio Fognini coming through an all-Italian battle with the 15th-ranked Andreas Seppi, 3-6 6-4 6-4.
Ninth seed Marin Cilic went through, seeing off Horacio Zeballos in three sets, while big-serving Milos Raonic dropped just five games in getting the better of Julien Benneteau.
France’s Benoit Paire was a winner over Ivan Dodig and Jarko Nieminen saw off Victor Troicki, while other first-round games brought about victories for Nikolay Davydenko and Mikhail Youzhny.
In qualifying, Pablo Andujar and Edouard Roger-Vasselin secured wins.
Rafael Nadal is the defending champion – he starts later in the week – and is chasing a staggering ninth trophy in a row in the principality. He is seeded number three, however, as a result of his injury problems.