It is their first meeting with the German side, who are in the knockout stages for the first time in their short history.
Here, the PA news agency takes a closer look at the Bundesliga outfit.
Red Bull co-owner Dietrich Mateschitz was desperate to involve his company in German football and after a three-and-a-half-year search bought SSV Markranstadt in 2009. The dream was to take them to the top of the Bundesliga and it has taken them a little over 10 years. With plenty of resources, there were four promotions in seven years and they are now regular challengers for domestic honours. Much like the inception of MK Dons in England, their rise has not been met with widespread approval by football purists in Germany, but the owners, who named the club RasenballSport Leipzig to circumvent advertising laws, turned them into one of the biggest clubs in the country.
If speculation were true, Nagelsman could have been in the Tottenham dugout for this match, as the 32-year-old was reportedly considered as a replacement for Mauricio Pochettino. Jose Mourinho ended up being the man chosen, but the fact Nagelsman was linked shows how high his stock is in European football. After his playing career was ended as a teenager due to injury, he became the youngest manager in Bundesliga history when he took over at Hoffenheim aged 28 in 2016 – earning him the nickname Baby Mourinho. He took them to the Champions League for the first time in their history and was appointed at Leipzig last summer, with the remit to turn them into a force on the European stage.
There are a couple of familiar names in the Leipzig squad in the shape of Ademola Lookman and Nathan Ampadu. Lookman signed last summer for a fee of £22.5million having initially enjoyed a loan spell in 2018, where he scored five goals in 11 games. Things have been tougher since his permanent move, however, as for a variety of reasons he has played just seven times this season and was linked with a move away in the January transfer window. Chelsea defender Nathan Ampadu is on a season-long loan and has struggled for game time. However, a defensive crisis has seen him given a chance, with his appearance in the weekend win over Werder Bremen just his sixth of the campaign.
Leiozig are in unchartered waters as Wednesday's first leg against Spurs will be their first ever Champions League knockout game. Their only ever previous season in Europe's premier club competition came in 2017/18 where they went out in the group stage and ended up reaching the Europa League quarter-final. After exiting at the group stage of the Europa League last season, they finally got their act together this term, finishing top of a pool that included Lyon, Benfica and Zenit St Petersburg. They got 11 points, winning three and drawing two.