On March 11, 2010, Pope Benedict XVI appointed Seitz auxiliary bishop of Dallas with the titular see of Cozyla. He said: "I have learned through the years that following Christ is an adventure filled with totally unexpected dips and turns. When you give your life to His service you better learn to enjoy the ride." Along with J. Douglas Deshotel, he was be one of the first auxiliary bishops of the Dallas since the Diocese of Fort Worth was split from it in 1969. He received his episcopalconsecration on the April 27, 2010 from Bishop Kevin Farrell, with Charles V. Grahmann and Michael Duca serving as co-consecrators.
On May 6, 2013, Pope Francis appointed Seitz the Bishop of El Paso, Texas. He was installed there on July 9, 2013. Bishop Seitz is an advocate for the humane treatment of migrants, refugees, and asylum seekers arriving at the border. On June 27, 2019, he performed a public action in which he and members of the Hope Border Institute escorted seven Central American asylum seekers to the Santa Fe international bridge in Ciudad Juárez in order to assist them in claiming asylum. On July 18, 2017, he issued a pastoral letter on immigration in which he said that "elected leaders have not yet mustered the moral courage to enact permanent, comprehensive immigration reform" and praised the efforts of the "heroic individuals, families, pastors, religious, parishes and institutions that spend themselves in service to migrants and refugees" and campaign "against the militarization of our border". He expressed concern for immigrant families who fear separation and for law enforcement officers who "put their lives on the line to stem the flow of weapons and drugs" but are "troubled in conscience by divisive political rhetoric and new edicts coming from Washington, D.C." He condemned profit-based immigrant detention centers, the hostility shown to asylum seekers, and "the disparagement of our Muslim brothers and sisters". In the aftermath of the El Paso Walmart shooting on August 3, 2019, Bishop Seitz wrote a pastoral letter on racism and white supremacy in which he wrote that, "If we are honest, racism is really about advancing, shoring up, and failing to oppose a system of white privilege and advantage based on skin color. When this system begins to shape our public choices, structure our common life together and becomes a tool of class, this is rightly called institutionalized racism. Action to build this system of hate and inaction to oppose its dismantling are what we rightly call white supremacy. This is the evil one and the ‘father of lies’ incarnate in our everyday choices and lifestyles, and our laws and institutions." The pastoral letter invokes the history of racism in the United States, especially the history of colonialism and racial terror at the US-Mexico border. It calls on Catholics to fight against racism and acknowledges support from the Catholic Church in the United States for an assault weapons ban. In February 2020, Bishop Seitz, along with bishops from Texas, Arkansas, and Oklahoma, met with Pope Francis in Rome. Pope Francis gave Bishop Seitz 50 rosaries that he personally blessed for survivors of the El Paso Walmart shooting.