The first semi-final took place on 6 February 2016 at the Scandinavium in Gothenburg, hosted by Gina Dirawi and Petra Mede. "Don't Worry" performed by Ace Wilder and "Constellation Prize" performed by Robin Bengtsson qualified directly to the final, while "Bada nakna" performed by Samir and Viktor and "Rik" performed by Albin and Mattias advanced to the Second Chance round. A total of 4,389,687 votes were cast by the viewers during the show with a total of 477,689 SEK collected for Radiohjälpen.

In addition to the performances of the competing entries, Dirawi and Mede opened the show with a performance titled "Hela Sveriges fest" (English: All of Sweden's party) and performed together with Lasse Kronér as part of the interval act in a number titled "Allt är Eurovisions fel" (English: It's all Eurovision's fault). Spanish girl group and 2006 Spanish Eurovision entrants Las Ketchup also performed their song "The Ketchup Song (Aserejé)" as an interval act. Recurring interval acts such as Jonas Gardell's schlager school and dramatic readings of past Melodifestivalen song lyrics by Swedish actors were also part of the programme; Stina Ekblad performed a dramatic reading of Samir and Viktor's Melodifestivalen 2015 entry "Groupie".

Two days prior to the semi-final on 4 February, "Himmel för två", performed by Anna Book, was disqualified after it was discovered that the song had previously been entered and performed in the audition round of the 2014 Moldovan Eurovision Song Contest national selection. Book performed the song during the semi-final as an interval act