Officials said Biden and Emhoff stayed to watch the Astros take on the Orioles. They also made an appearance on the club's television and radio broadcasts.
The event, part of Major League Baseball's Vaccinate at the Plate program, was free to all fans.
This the third vaccination event the Astros have hosted for the community.
Under the MLB's program, all 30 clubs host at least one event.
Meanwhile, Biden and Emhoff have been touring the nation to promote COVID-19 vaccinations.
Last week, Biden stopped in Nashville to appear with country singer Brad Paisley while Emhoff recently toured Memphis, Birmingham and Chicago.
Biden will stop in Dallas to tour a vaccination site at a school with former Dallas Cowboy and Football Hall of Famer Emmitt Smith before traveling to Houston with Emhoff.
The first lady and second gentleman's visit was announced over the weekend.
Houston Mayor Sylvester Turner spoke at a vaccine clinic Saturday hosted by the Fountain Life Center. He stressed the importance of their visit and praised the city for finding different ways to administer the vaccine by going where the people are.
"We are finding creative ways of getting it out, and I think they recognize that and that's the reason why they've added Houston to their list," Turner said.
Turner reminded Houstonians that vaccines are still available and encouraged everyone to continue wearing masks.
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