(1) Background: To assess time trends in the incidence and in-hospital outcomes of urinary tract infection (UTI) in older people (≥65 years) in Spain (2001–2018) according to sex and to identify the factors independently associated with in-hospital mortality (IHM). (2) Methods: Using the Spanish National Hospital Database, we analyzed comorbidity, procedures, diagnosis, isolated microorganisms, and outcomes. (3) Results: We included 583,693 admissions (56.76% women). In both sexes, the incidence increased with age over time (p < 0.001). In men and women, the highest IHM was found among the oldest patients (>84 years) with values of 9.16% and 8.6%, respectively. The prevalence of bacteremia increased from 4.61% to 4.98% from 2001 to 2018 (p < 0.001) and sepsis decreased from 3.16% to 1.69% (p < 0.001). The risk of dying increased with age (>84 years) (OR 3.63; 95% CI 3.5–3.78) and with almost all comorbidities. Urinary catheter was a risk factor for women (OR 1.1; 95% CI 1.02–1.18) and protective for men (OR 0.71; 95% CI 0.66–0.76). Isolation of Staphylococcus aureus increased the risk of IHM by 40% among men (OR 1.4; 95% CI 1.28–1.53). After adjusting for confounders, IHM decreased over time. (4) Conclusions: The incidence of UTIs was higher in older patients and increased over time; however, IHM decreased during the same period. Female sex, age, comorbidities, sepsis, and a Staphylococcus aureus isolation increased risk of IHM.