The story revolves around a generational conflict between a partially estranged father and daughter, old-fashioned working-class George (George Lopez) and his Gen Z daughter Maya (Mayan Lopez). George was largely an absent father, cheating on Maya's mother (Leyva) and gambling a lot. Now Maya has had years of therapy and George has had a rough time. Now that he has moved in with Maya and her family, the two may have a chance to mend their relationship. Together with his stoner friend Oscar (Madrigal), George renovates Maya's kitchen and enjoys tormenting her husband Quinten (Shively). George also bonds with his young grandson, Chance (Gonzalez).

The first season of Lopez vs. Airing primarily on Friday nights, Lopez averaged 0.27 in the 18-49 demographic and 1.98 million viewers in the live+same day ratings (including DVR playback until 3:00 AM). It was one of NBC's lower-rated scripted series of the season, but still performed decently for a Friday night series. In the live+7-day viewing figures, the sitcom only gained 20% more viewers.
The Peacock Network has revealed its plans for the 2023-24 broadcast year, and we now know that Lopez vs. Lopez will not return until midway through the season. A specific start date for season two is expected later this year.