Later when presenting a segment from an empty ITV studio next to the Saturday Night Takeaway's, Dec joked not to worry - "It's not going that badly".
This will be the first time in 20 years that Dec has had to present without Ant by his side, so he's understandably feeling the pressure ahead of tonight's show.
Scarlett Moffatt and Stephen Mulhern will be on hand in their regular support roles. The shift in line-up was alluded to a number of times during the broadcast, thanks in large part to Merchant who offered to exit his lofty recording booth and join Dec in front of the audience: "I can't help but notice a little bit of space on the stage there. Have a great Good Friday! D x".
Saturday Night Takeaway bosses 'in a panic' on how to address Ant's absence
He thanked them for their "very, very, warm reception", before adding: "I've got twice the amount of work to do so we're going to crack on and say hello to our star guest announcer Mr Stephen Merchant".
It was confirmed in a tweet last week from Ant and Dec's official account that tonight's episode and the Florida finale would both be hosted by Dec on his own.
Dec didn't mention his co-presenter's absence directly this evening, but thanked viewers for "all of their support" at the end of the show.
Reid wrote: "He's really easing into it and getting more comfortable as he realises how much the audience is with him".
"@SamdySonxxxxx posted: "@antanddec @itvtakeaway Dec you did yourself & Ant proud, it was a fabulous but emotional show, keep smiling. looking forward to next week".
The 42-year-old presenter will also present next week's episode, the final one in the current series from Florida.
Tonight's show is the first to air since Ant checked into rehab, following his arrest for drink driving last Wednesday.
McPartlin will appear in court on April 4.