The Scot averaged 100.91 to move through, and afterwards admitted the clash with Littler would be a special moment.
"I'm buzzing to play, in my opinion, the best darts player in the world," Menzies said.
"I'm a massive fan of Luke Humphries, but I feel Littler right now is the man. To play him up here on this stage tomorrow will be an experience, and I'm looking forward to it."
Dirk van Duijvenbode also advanced, surviving a spirited comeback from Norway's Cor Dekker to prevail 6-4 after racing into a 4-0 lead. His reward is a meeting with reigning champion Humphries, who begins his title defence on Saturday at the PVA Expo.
Former World Matchplay champion Nathan Aspinall marked his PDC return with a resounding 6-0 victory over local qualifier Jiri Brejcha.
It was his first competitive outing since July, and he admitted rust had crept into his game despite the emphatic scoreline.
"It felt good to be back up here after not playing for a while," Aspinall reflected.
"The rhythm was awful, my throw was terrible; I could tell I hadn't played darts for seven weeks. I need to be better tomorrow, otherwise I'll get hammered by James."
His next opponent will be world number five James Wade.
Elsewhere, Belgium's Mike De Decker impressed with a 100.9 average in a 6-3 success against European Champion Ritchie Edhouse.
That result sets up a difficult second-round clash with Michael van Gerwen, though De Decker believes a recent equipment change has given him new confidence.
"This week I changed back to my old set-up and everything feels more comfortable," he said.
"We all know what Michael's been through this year. I get along with him very well. We will see tomorrow, if the best version of Michael turns up, I'm in for a tough task."
Peter Wright faces Slovenia's Benjamin Pratnemer, who claimed the scalp of German number two Ricardo Pietreczko.
Krzysztof Ratajski made light work of Raymond van Barneveld in a one-sided 6-1 victory, tightening his grip on a provisional World Grand Prix qualification spot. William O'Connor, meanwhile, edged past Luke Woodhouse 6-5 to enhance his own qualification hopes.
The second round continues on Saturday with winners progressing to Sunday's third round, before the tournament concludes with quarter-finals, semi-finals and the final in an action-packed evening session.