During the 1800s, Fort Wayne continued to grow and thrive. The Wabash and Erie Canal played a key role in this city's development. Completed in 1853 after over a decade of construction, it stretched from Toledo, Ohio to the Ohio River, running through Fort Wayne. In the 1850s, railroads arrived in Fort Wayne, which furthered the city's growth. As railroads were faster, they soon overtook business from the canal, eventually making it obsolete.
Passenger travel peaked at the station during World War II; around 3,000 people passed through every day. Numerous political and social events took place at the station over the years including presidential campaign whistle-stops, and the annual arrival of Santa Claus.
Passenger service began to steadily decline in the 1950s as people used cars trucks more and more. As stated above, Amtrak was the station's last tenant, ending operations in 1990. The building remained vacant until 1996 when work to renovate it began.