St. Joseph is a city mostly in and county seat of Buchanan County, Missouri, United States. A small portion of the city extends north into Andrew County. Located on the Missouri River, it is the principal city of the St. Joseph Metropolitan Statistical Area, which includes Buchanan, Andrew, and DeKalb counties in Missouri and Doniphan County, Kansas. As of the 2020 census, St. Joseph had a total population of 72,473, making it the 8th most populous city in the state, and the 3rd most populous in Northwest Missouri. St. Joseph is located roughly thirty miles north of the Kansas City, Missouri, city limits and approximately 125 miles (201 km) south of Omaha, Nebraska.

The city was named after the town's founder Joseph Robidoux and the biblical Saint Joseph. In the nineteenth century, it was the death place of American outlaw Jesse James. It was also the starting point of the Pony Express serving the West. Today, St. Joseph is home to Missouri Western State University, which enrolls over 3,800 students.

St. Joseph was founded on the Missouri River by Joseph Robidoux, a local fur trader of French Canadian descent. It was officially incorporated in 1843. In its early days, it was a bustling outpost and rough frontier town, serving as a last supply point and jumping-off point for travelers on the Missouri River toward the "Wild West". It was the westernmost point in the United States accessible by rail until after the American Civil War, which helped earn it the designation "Gateway to the West."

The main east–west downtown streets were named for Robidoux's eight children: Faraon, Jules, Francois (Francis), Felix, Edmond, Charles, Sylvanie, and Messanie. The street between Sylvanie and Messanie was named for his second wife, Angelique.

St. Joseph, or "St. Joe", as it was called by many, was a "Jumping-Off Point" for those migrants headed to the Oregon Territory in the mid-1800s. Such cities, including Independence, and St. Joseph, were where pioneers would stay and purchase supplies before they headed out in wagon trains across the Great Plains. The town was a very lively place.

Between April 3, 1860, and late October 1861, St. Joseph was one of the two endpoints of the Pony Express, which operated for a short period over the land then inaccessible by rail, to provide fast mail service. Today the Pony Express Museum hosts visitors in the former stables of the company. St. Joseph is identified by the slogan, "Where the Pony Express started and Jesse James ended."

The town's main hotel was Patee House. In the post-Civil War years, when the economy was down, the hotel was used for a time by the Patee Female College. It was occupied by the St. Joseph Female College up to 1880.

In 1874 the State Lunatic Asylum #2 was opened just East of St. Joseph. The asylum, originally built for 250 patients, opened its doors with more than 300. The asylum was mostly self-sustaining with three large farms, power plant, fire department, metal shops, wood shops, dairy and more, all worked by the patients. Over the decades the asylum grew rapidly, reaching its peak of close to 3,000 patients by the 1940s. In 1968 occupational therapist George Glore, with the help of his patients, recreated several historic treatment devices for Mental Health Awareness Month. This was the start of the Glore Psychiatric Museum. Now the largest museum of its kind in the world, the museum shows the history mental health treatment and still houses the original exhibits created by George Glore and his patients.