It was founded in 1929 by the merger of Elberfeld, Barmen, Ronsdorf, Cronenberg and Vohwinkel, and was initially called "Barmen-Elberfeld" before adopting its present name in 1930.

Wuppertal is located between the Ruhr (Essen) to the north, Düsseldorf to the west, and Cologne to the southwest, and over time has grown together with Solingen, Remscheid and Hagen.

The Wupper Valley was, along with the Ore Mountains and before the Ruhr, the first highly industrialized region of Germany, which resulted in the construction of the Wuppertal Schwebebahn suspension railway in the then independent cities of Elberfeld and Barmen.

Wuppertal in its present borders was formed in 1929 by merging the industrial cities of Barmen and Elberfeld along with the communities of Vohwinkel, Ronsdorf, Cronenberg, Langerfeld and Beyenburg.

However, a large number of historic sites have been preserved, such as: The US 78th Infantry Division under Major General Edwin P. Parker Jr. captured Wuppertal against scant resistance on 16 April 1945.

Population numbers during these times of as-yet unparalleled growth peaked at about 423,000 in 1963; in the 1970s, a period of steady decline followed in the wake of industrial losses.

As of 31 December 2022, the largest groups of foreign residents were: In total, Wuppertal possesses over 4,500 buildings classified as national monuments, most exemplifying styles such as Neoclassicism, Eclecticism, Historicism, Art Nouveau/Jugendstil and Bauhaus.

The American TV station CNN recommended Wuppertal as one of 20 places worldwide to visit in the year 2020 because of the Schwebebahn, the architectural diversity and the Nordbahntrasse, a 22-kilometre (14 mi) cycle route across the city 2020.

In their first season in the nationwide first division, the club reached a remarkable fourth place and qualified for the UEFA Cup for the first and only time in its history.

After a first-round defeat by Polish side Ruch Chorzów and another two widely unsuccessful Bundesliga campaigns, the club disappeared from the top flight again, though, and has yet to return.

The additional "Borussia" was scrapped again during 2013 due to fans' demand amidst a change of leadership which was brought about to lead the club through necessary insolvency proceedings which have been completed as of September 2014.

In handball, Wuppertal's most successful team is Bergischer HC, playing in the top-tier Handball-Bundesliga which they were promoted to for the second time during 2013, reaching 15th place during the 2013–14 campaign and therefore staying among the top scorers for a second consecutive season.

BHC originates from a 2006 cooperation between the management, squad and main sponsor of LTV Wuppertal and rivals SG Solingen from the nearby city of the same name.

LTV spent most of their seasons in the second and third tiers, before they merged with Wuppertaler SV's handball section in 1996 to form HSG LTV/WSV Wuppertal.

Reacting to low attendances, the eponymous Bayer AG decided to relocate the volleyball team to Wuppertal in 1992, where there also was a Bayer-funded club.

Presently, they once more play by the name of Bayer Wuppertal in the third-tier Regionalliga, unable to promote with their current financial set-up.

A year later, they narrowly missed out on back-to-back trebles, losing to French side CJM Bourges in the newly christened EuroLeague's final.

In 2002, the club withdrew from the Bundesliga due to financial troubles, their then-main sponsor Gold-Zack Werke filing for insolvency a year later.

The privately financed Junior Uni is a unique German initiative to educate youth from the age of 4 to 18 in science outside the school program.

In 1950, a young elephant named Tuffi was put aboard the Wuppertal Schwebebahn (monorail), as a promotion for the Althoff Circus.