Clinical finishing proved to be the difference for world number 15 Webster, as Cross exited the Blackpool event in round two for a second successive year.
With Cross waiting on a finish at 10-8, the Norfolk thrower sealed victory with his last dart in hand to spark huge celebrations in the Winter Gardens and keep himself in the hunt to claim the Phil Taylor Trophy.
"I really enjoyed that win, it's a great feeling to beat the World Champion," said Webster, who also reached the quarter-finals of the 2018 World Championship.
"When you get involved in a scrap you have to dig in and win it. I know I'm good enough to beat the best players and now I'm showing it.
"I've got the chance of a lifetime to push into the top ten and now I want to keep winning and keep pushing my way up.
"I'm playing the best darts of my life in terms of results but I've still got an extra 20% of my practice game to bring to the big stage.
"I didn't used to like playing against Mensur but I enjoy it now so I'm looking forward to getting stuck into that game."
There was nothing to separate the pair with the scores tied at 5-5 but it was Webster who seized the initiative in the second half of the contest, taking out 20 to take a 7-5 lead.
That break of throw turned out to be the crucial moment in the match as Webster stood firm to hold throw four times despite the best efforts of Cross, who averaged 98.81 but paid for 21 missed doubles.
Having won through to his latest televised quarter-final, the Norfolk man who will face Mensur Suljovic in the last eight on Friday.
Austrian ace Suljovic edged out Ian White 11-8 in a tense affair to reach the quarter-finals for the third time in four years.
The world number six got off to a strong start, taking a 3-0 lead before maintaining the advantage throughout the game despite being pushed all the way by White, who clawed his way back into the contest to trail 9-8.
Suljovic crucially found double nine at the third attempt to break straight back before pinning his favourite double 14 in the following leg to book his place in the last eight once again.
"My performance was not that good, but I am so happy that I won," said Suljovic, the 2017 Champions League of Darts winner.
"It was a very hard game, Ian is a good player. There are lots of good players in this tournament who are favourites ahead of me but I will keep trying my best to win."
Last year's beaten finalist Peter Wright produced a superb 105.6 average, the highest of the tournament so far, in his 11-5 victory over Kim Huybrechts.
The world number two was in confident mood heading into the tie and delivered a world-class performance, though Huybrechts matched his rival as both players averaged over 105 after nine legs.
Wright broke the Belgian's throw to move into a 7-4 lead and then cruised to victory, landing a roof-raising 130 finish on the bull on the way to booking a quarter-final tie with Simon Whitlock.
"I felt comfortable and I felt focused - I'm happy with how I played," said Wright.
"In my next game it will be tough because Simon is a good friend but when we get up on stage I will have to treat him as the enemy. He is fantastic though and he's playing really good darts at the moment."
Whitlock's 11-7 win over James Wade in the opening game of the evening guaranteed a new name on the trophy this year.
Wade, the only former champion remaining in the field following his 2007 triumph, struggled to find his best form throughout the match but stuck with Whitlock and found himself trailing 6-4 heading into the second break.
Two-time Winter Gardens semi-finalist Whitlock took advantage of Wade's two missed darts at double to go within a leg of victory at 10-7 and then finished the job to advance to the quarter-finals in Blackpool for the first time since 2014.
"I feel really relaxed on the Winter Gardens stage this year, I'm enjoying playing up there," said Whitlock.
"I started well and then it became a scrap, I felt like I should've been further ahead at some points but I got the win and that's all that matters.
"The last time I got to the semis here was in 2014 and I actually feel like I'm playing better now than I was then."
The £500,000 tournament continues on Thursday at Blackpool's Winter Gardens, as world number four Gary Anderson plays Joe Cullen and Dave Chisnall plays Jeffrey de Zwaan, the Dutch wonderkid who has knocked out Michael van Gerwen and Adrian Lewis so far this week.
Friday's quarter-finals begin with Suljovic meeting Webster before Wright takes on Whitlock for a spot in the last four.
2018 BetVictor World Matchplay
Schedule of Play
Wednesday July 25
Simon Whitlock 11-7 James Wade
Mensur Suljovic 11-8 Ian White
Darren Webster 11-8 Rob Cross
Peter Wright 11-5 Kim Huybrechts
Thursday July 26 (7pm)
Jeffrey de Zwaan v Dave Chisnall
Joe Cullen v Gary Anderson
Friday July 27 (7pm)
Peter Wright v Simon Whitlock
Mensur Suljovic v Darren Webster
Quarter-Finals: Best of 31 legs