Hijo del escribano español Bartolomé González de Villaverde y de María de Santacruz. Nació en la pequeña población de Asunción, en el actual Paraguay, en 1576. Como sus hermanos, eran nueve, desde pequeño aprendió a hablar tanto español como guaraní, así como a trabajar la tierra, lo que luego le sería de gran utilidad en su ulterior labor evangelizadora.
Roque, en 1585 y 1586, estudió en un seminario improvisado en el coro de la catedral por el obispo dominico Francisco Guerra. Después, sin el seminario, le formó el padre Lorenzana, rector del colegio de la Compañía en Asunción, que enseñaba Moral y algo de Teología al clero.
Vacante la diócesis, la visitó fray F. de Trejo y Sanabria, obispo de Tucumán, conoció a Roque y le rogó que aceptase ser ordenado sacerdote y lo fue en diciembre de 1598, convirtiéndose en uno de los primeros sacerdotes que fueron ordenados en el Río de la Plata. Su maestro en pastoral indígena, el franciscano Luis de Bolaños, se alegró de que así fuera. De hecho, al principio, su labor pastoral se centró en la atención a los indígenas.
En 1609 llegó el dominico fray Reginaldo de Lizárraga, y el nuevo obispo nombró vicario general a Roque González. Éste inició su noviciado en el colegio de la Compañía de Jesús, y antes de acabarlo, a ruego de autoridades civiles y eclesiásticas, calmó a los guacurús que atacaban Asunción.
En 1611 llegó a una reducción, iniciada por franciscanos, dejada por ataques de guaraníes, y otra vez iniciada con pocos guaraníes hartos de guerra. Así los jesuitas comenzaron a evangelizar el Paraná en 1610.
El padre Roque comprendió bien las relaciones entre los caciques parientes y utilizando estos contactos empezó a evangelizar gracias a guaraníes ya evangelizados, de modo que comunicaba cada reducción con la más próxima; como el padre Antonio Ruiz de Montoya en el Guayrá y el padre Boroa en el Paraná, el padre Roque inició la evangelización por el río Uruguay, convirtiéndose en superior de todas las misiones que coordinaba en 1626. Su ingente labor misionera comenzó en la reducción de San Ignacio de Loyola. En ella los indios aprendían trabajos manuales y las primeras letras, y se les instruía en la doctrina católica. El padre Roque, además de la labor evangelizadora, era un solícito promotor de su vida económica y social.
Más adelante fundó otras diez reducciones.
Pero tras la imprudente intervención de un funcionario que envió el gobernador desde Buenos Aires para administrar una reducción (algo imprevisto), que golpeó a un cacique, un chamán, ante tal abuso, amenazó a quien no le obedeciera, y fueron víctimas quienes a través del provincial habían retirado al funcionario impertinente: los padres Roque, Alonso Rodríguez, Juan del Castillo y un anciano cacique guaraní catecúmeno que recibió a los padres Roque y Alonso, y defendió la evangelización el 15 de agosto de 1628. Los tres jesuitas ya fueron canonizados, y la causa del anciano cacique está iniciada en base a haber muerto por el Evangelio en idénticas circunstancias (bautismo de sangre) y con nombre guaraní que muestra valentía al manifestar su fe: Ará sunú, voz del cielo.
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